{"id":16868,"date":"2026-05-15T12:23:47","date_gmt":"2026-05-15T12:23:47","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=blog&#038;p=16868"},"modified":"2026-05-15T12:36:31","modified_gmt":"2026-05-15T12:36:31","slug":"preclinical-models-of-substance-use-withdrawal","status":"publish","type":"blog","link":"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/preclinical-models-of-substance-use-withdrawal\/","title":{"rendered":"Substance Use Withdrawal: How Preclinical Models Inform Treatment Development"},"content":{"rendered":"\n<div x-data='subNav({\"anchor_map\":{\"https:\\\/\\\/www.sygnaturediscovery.com\\\/blog\\\/drug-addiction-a-public-health-issue\\\/\":\"Part 1: Introduction\",\"https:\\\/\\\/www.sygnaturediscovery.com\\\/blog\\\/substance-use-intoxication-binge-insights-from-preclinical-models\\\/\":\"Part 2: Intoxication \",\"https:\\\/\\\/www.sygnaturediscovery.com\\\/blog\\\/preclinical-models-of-substance-use-withdrawal\\\/\":\"Part 3: Withdrawal\",\"https:\\\/\\\/www.sygnaturediscovery.com\\\/blog\\\/preclinical-models-of-craving-and-relapse\\\/\":\"Part 4: Craving\"}})' id=\"pegasus-subnav\" class=\"SubNav w-full text-content-tertiary \" false x-cloak style=\"\">\n    <div x-ref=\"fixedNav\" class=\"SubNav__bar w-full h-[var(--subnav-height)] z-page-header whitespace-nowrap border-t border-grey-200 container flex items-center justify-between shadow-sm\">\n\n                    <!-- Desktop Navigation (tablet and up) -->\n            <div class=\"flex items-center min-w-0 flex-1 mr-4\">\n                                    <div class=\"flex items-center gap-x-3 mr-4 sm:mr-8 pr-4 sm:pr-8 md:border-r md:border-grey-200 flex-shrink-0\">\n                        \n                                                    <a href=\"https:\/\/www.sygnaturediscovery.com\/in-vivo-pharmacology\/cns-and-pain-models\/\" class=\"wp-block-button wp-block-button is-style-back-chevron text-content-primary \">\n                                <span class=\"wp-block-button__link wp-element-button bg-ivory-300 text-content-primary rounded-full\">CNS &amp; Pain Models<\/span>\n                            <\/a>\n                                            <\/div>\n                \n                <div class=\"hidden md:block min-w-0 flex-1 overflow-hidden relative\">\n                    <div class=\"nav-container-wrapper\">\n                        <ul x-ref=\"navList\" class=\"flex flex-row items-center !m-0 !list-none gap-8 !py-4 overflow-x-auto scrollbar-hide pr-16\">\n                                                            <li class=\"!m-0 !p-0 !list-none flex-shrink-0\">\n                                    <div class=\"wp-block-button is-style-text-link\">\n                                        <a href=\"https:\/\/www.sygnaturediscovery.com\/blog\/drug-addiction-a-public-health-issue\/\" class=\"wp-block-button__link wp-element-button has-text-sm-font-size px-2 whitespace-nowrap after:bg-transparent \" :class=\"currentLink === 'https:\/\/www.sygnaturediscovery.com\/blog\/drug-addiction-a-public-health-issue\/' || 'https:\/\/www.sygnaturediscovery.com\/blog\/drug-addiction-a-public-health-issue\/' === window.location.href ? '-active' : ''\">\n                                            Part 1: Introduction\n                                        <\/a>\n                                    <\/div>\n                                <\/li>\n                                                            <li class=\"!m-0 !p-0 !list-none flex-shrink-0\">\n                                    <div class=\"wp-block-button is-style-text-link\">\n                                        <a href=\"https:\/\/www.sygnaturediscovery.com\/blog\/substance-use-intoxication-binge-insights-from-preclinical-models\/\" class=\"wp-block-button__link wp-element-button has-text-sm-font-size px-2 whitespace-nowrap after:bg-transparent \" :class=\"currentLink === 'https:\/\/www.sygnaturediscovery.com\/blog\/substance-use-intoxication-binge-insights-from-preclinical-models\/' || 'https:\/\/www.sygnaturediscovery.com\/blog\/substance-use-intoxication-binge-insights-from-preclinical-models\/' === window.location.href ? '-active' : ''\">\n                                            Part 2: Intoxication \n                                        <\/a>\n                                    <\/div>\n                                <\/li>\n                                                            <li class=\"!m-0 !p-0 !list-none flex-shrink-0\">\n                                    <div class=\"wp-block-button is-style-text-link\">\n                                        <a href=\"https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-substance-use-withdrawal\/\" class=\"wp-block-button__link wp-element-button has-text-sm-font-size px-2 whitespace-nowrap after:bg-transparent \" :class=\"currentLink === 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-substance-use-withdrawal\/' || 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-substance-use-withdrawal\/' === window.location.href ? '-active' : ''\">\n                                            Part 3: Withdrawal\n                                        <\/a>\n                                    <\/div>\n                                <\/li>\n                                                            <li class=\"!m-0 !p-0 !list-none flex-shrink-0\">\n                                    <div class=\"wp-block-button is-style-text-link\">\n                                        <a href=\"https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-craving-and-relapse\/\" class=\"wp-block-button__link wp-element-button has-text-sm-font-size px-2 whitespace-nowrap after:bg-transparent \" :class=\"currentLink === 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-craving-and-relapse\/' || 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-craving-and-relapse\/' === window.location.href ? '-active' : ''\">\n                                            Part 4: Craving\n                                        <\/a>\n                                    <\/div>\n                                <\/li>\n                                                    <\/ul>\n                        \n                        <div x-ref=\"scrollIndicator\" class=\"scroll-indicator\" x-show=\"showScrollIndicator\" x-transition:enter=\"transition ease-out duration-500\" x-transition:enter-start=\"opacity-0 transform translate-x-full\" x-transition:enter-end=\"opacity-100 transform translate-x-0\">\n                            <svg class=\"chevron-icon w-4 h-4\" viewbox=\"0 0 16 16\" fill=\"none\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" aria-hidden=\"true\">\n                                <path d=\"M5.65306 3.53025L10.6531 8.53025C10.7227 8.60018 10.7775 8.68297 10.8154 8.77414C10.8533 8.8653 10.8735 8.96304 10.8735 9.06175C10.8735 9.16046 10.8533 9.2582 10.8154 9.34936C10.7775 9.44053 10.7227 9.52332 10.6531 9.59325L5.65306 14.5932C5.51217 14.7341 5.32107 14.8133 5.12181 14.8133C4.92255 14.8133 4.73145 14.7341 4.59056 14.5932C4.44966 14.4523 4.37051 14.2612 4.37051 14.062C4.37051 13.8627 4.44966 13.6716 4.59056 13.5307L9.06294 9.06175L4.59056 4.59325C4.44966 4.45236 4.37051 4.26126 4.37051 4.062C4.37051 3.86274 4.44966 3.67164 4.59056 3.53075C4.73145 3.38985 4.92255 3.3107 5.12181 3.3107C5.32107 3.3107 5.51217 3.38985 5.65306 3.53075V3.53025Z\" fill=\"currentColor\"><\/path>\n                            <\/svg>\n                        <\/div>\n                    <\/div>\n                <\/div>\n            <\/div>\n\n            <!-- Mobile menu button -->\n            <button x-ref=\"navMenuButton\" type=\"button\" class=\"flex justify-center items-center py-2 whitespace-nowrap pl-5 pr-2.5 ml-auto md:hidden\" aria-label=\"Show more navigation items\" :aria-expanded=\"mobileSubMenuOpen\">\n                <span class=\"sr-only pr-2 inline-block\">More<\/span>\n\n                <svg class=\"transition duration-500 ease-in-out\" :class=\"mobileSubMenuOpen ? 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'bg-blue-50 text-blue-700 font-medium' : ''\" false>\n                                        Part 1: Introduction\n                                    <\/a>\n                                <\/li>\n                                                            <li class=\"!m-0 !p-0 !list-none\">\n                                    <a href=\"https:\/\/www.sygnaturediscovery.com\/blog\/substance-use-intoxication-binge-insights-from-preclinical-models\/\" class=\"block px-4 py-3 rounded-lg text-sm text-gray-700 hover:bg-ivory-300 transition-colors duration-150 focus:outline-none focus:bg-ivory-300 focus:ring-2 focus:ring-inset focus:ring-blue-500 \" :class=\"currentLink === 'https:\/\/www.sygnaturediscovery.com\/blog\/substance-use-intoxication-binge-insights-from-preclinical-models\/' || 'https:\/\/www.sygnaturediscovery.com\/blog\/substance-use-intoxication-binge-insights-from-preclinical-models\/' === window.location.href ? 'bg-blue-50 text-blue-700 font-medium' : ''\" false>\n                                        Part 2: Intoxication \n                                    <\/a>\n                                <\/li>\n                                                            <li class=\"!m-0 !p-0 !list-none\">\n                                    <a href=\"https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-substance-use-withdrawal\/\" class=\"block px-4 py-3 rounded-lg text-sm text-gray-700 hover:bg-ivory-300 transition-colors duration-150 focus:outline-none focus:bg-ivory-300 focus:ring-2 focus:ring-inset focus:ring-blue-500 \" :class=\"currentLink === 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-substance-use-withdrawal\/' || 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-substance-use-withdrawal\/' === window.location.href ? 'bg-blue-50 text-blue-700 font-medium' : ''\" false>\n                                        Part 3: Withdrawal\n                                    <\/a>\n                                <\/li>\n                                                            <li class=\"!m-0 !p-0 !list-none\">\n                                    <a href=\"https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-craving-and-relapse\/\" class=\"block px-4 py-3 rounded-lg text-sm text-gray-700 hover:bg-ivory-300 transition-colors duration-150 focus:outline-none focus:bg-ivory-300 focus:ring-2 focus:ring-inset focus:ring-blue-500 \" :class=\"currentLink === 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-craving-and-relapse\/' || 'https:\/\/www.sygnaturediscovery.com\/blog\/preclinical-models-of-craving-and-relapse\/' === window.location.href ? 'bg-blue-50 text-blue-700 font-medium' : ''\" false>\n                                        Part 4: Craving\n                                    <\/a>\n                                <\/li>\n                                                    <\/ul>\n\n                                                    <div class=\"mt-10 pb-5 \">\n                                \n        <div class=\"wp-block-button SubNav__ctaButton wp-block-button btn-primary dark mb-4 sm:mb-0 rounded-full inline-flex\">\n            <a class=\"wp-block-button__link wp-element-button\" href=\"https:\/\/www.sygnaturediscovery.com\/contact\/\">Get in touch<\/a>\n        <\/div>\n        \n                            <\/div>\n                                            <\/div>\n                <\/div>\n            <\/div>\n            <\/div>\n<\/div>\n\n\n<h2 class=\"wp-block-heading has-text-2-xl-font-size\" style=\"padding-top:var(--wp--preset--spacing--50)\">Why Withdrawal is a Critical Phase of Substance Use Disorders <\/h2>\n\n\n\n<p>Prolonged exposure to a drug causes the body to adapt, resulting in drug users consuming higher quantities to experience the same effects, a process known as tolerance. When drug exposure is suddenly reduced or stopped, the physiological adaptations lead to withdrawal \u2013 a collection of unpleasant and sometimes dangerous symptoms.<\/p>\n\n\n\n<p>A mild version of these symptoms can be observed in heavy caffeine (classified as mildly to moderate addictive) consumers who can be irritable in the morning until they\u2019ve had a cup of coffee. This unpleasant experience can be alleviated by resuming drug use, reinforcing the addictive cycle. As a result, reducing withdrawal severity is a potential target for treating substance use disorders.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-text-2-xl-font-size\">Modelling Drug Dependence in Preclinical Studies <\/h2>\n\n\n\n<p>It is possible to model how the body adapts to prolonged drug exposure (dependence) and withdrawal in animal models. In contrast to intoxication models, withdrawal studies typically involve <strong>non-contingent drug administration<\/strong>, where a scientist administers the drug over an extended period.<\/p>\n\n\n\n<p>When drug administration is abruptly stopped, a characteristic set of symptoms are induced which can be scored using manual observation or by video and behavioral analysis software.<\/p>\n\n\n\n<h3 class=\"wp-block-heading has-text-xl-font-size\">Key Design Considerations <\/h3>\n\n\n\n<p>Two critical factors must be carefully controlled when designing a preclinical withdrawal model:<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Ensuring sufficient drug exposure to induce dependence<\/strong><\/li>\n<\/ol>\n\n\n\n<p style=\"padding-left:var(--wp--preset--spacing--30)\">Drug exposure during the dosing phase must remain high enough to induce physiological dependence. This can be achieved in several ways: <\/p>\n\n\n\n<ul style=\"padding-right:var(--wp--preset--spacing--30);padding-left:var(--wp--preset--spacing--60)\" class=\"wp-block-list\">\n<li><strong>Long half-life compounds, <\/strong>where daily dosing maintains sufficient exposure <\/li>\n\n\n\n<li><strong>More frequent dosing schedules <\/strong>for rapidly metabolized drugs <\/li>\n\n\n\n<li><strong>Osmotic pumps, <\/strong>which deliver a continuous dose over days, weeks or months via subcutaneous implantation<\/li>\n<\/ul>\n\n\n\n<p>2. <strong>Ensuring drug exposure is stopped abruptly to trigger withdrawal<\/strong><\/p>\n\n\n\n<p style=\"padding-left:var(--wp--preset--spacing--30)\">To induce this state, drug exposure must be stopped suddenly. This is straightforward for short half-like compounds, where cessation rapidly leads to declining drug levels.<\/p>\n\n\n\n<p style=\"padding-left:var(--wp--preset--spacing--30)\">However, challenges arise with long half-life drugs or osmotic pump delivery, where residual drug slowly tapers in the body, preventing overt withdrawal. In these cases, withdrawal can be <strong>pharmacologically<\/strong> <strong>precipitated<\/strong> by administering a drug that blocks the effect of the first drug. An example is using naloxone to block opioid receptors following morphine exposure.<\/p>\n\n\n\n<p style=\"padding-left:var(--wp--preset--spacing--30)\">While precipitated withdrawal can be effective, it introduced additional pharmacology that may not be ideal when assessing novel pharmaceutical treatments.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-text-2-xl-font-size\">Using Withdrawal Models to Evaluate Novel Treatments <\/h2>\n\n\n\n<p>Preclinical models of dependence and withdrawal can be applied at two stages:<\/p>\n\n\n\n<ul style=\"padding-left:var(--wp--preset--spacing--30)\" class=\"wp-block-list\">\n<li><strong>During the dosing phase, <\/strong>to assess whether treatment reduces the development of dependence<\/li>\n\n\n\n<li><strong>During withdrawal, <\/strong>to determine whether a treatment alleviates symptoms<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading has-blue-300-color has-text-color has-link-color has-text-2-5-xl-font-size wp-elements-9cbe32731a49d2bdbcedc2a10bfcc87a\" style=\"padding-top:var(--wp--preset--spacing--50)\"><strong>Case Study: Modelling Opioid Withdrawal and Methadone Maintenance Therapy <\/strong><\/h2>\n\n\n\n<p><strong> <\/strong>At Sygnature Discovery, we evaluated whether methadone would prevent rats from experiencing symptoms following prolonged morphine exposure. In the clinic, methadone is used as an opioid maintenance therapy, allowing people that have been using opioids, such as heroin and fentanyl, to transition to a safer opioid without experiencing severe withdrawal. We validated our model with a clinically relevant control so that it can be utilized in assessing efficacy of novel treatments.<\/p>\n\n\n\n<p>To induce dependence, rats were administered with morphine (30 mg\/kg) twice a day for 16 days. From day 17, rats were assigned to one of three treatment groups: continued morphine, saline, or methadone (20 mg\/kg, twice daily). Throughout both the dosing and cessation phases, body weight, food and water intake were measured daily. In addition, a scientist observed each rat and scored a list of 45 behaviors daily.<\/p>\n\n\n\n<p>Rats that were administered saline during the withdrawal phase consumed much more food (hyperphagia) and water (hyperdipsia) than rats not experiencing morphine dependence. They also showed behaviors that are linked to poor health and stress in rats.<\/p>\n\n\n<section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard  has-ivory-000-border-color is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"   border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px;border-width:10px;\">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-000-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<div class=\"wp-block-columns has-global-padding is-layout-constrained wp-block-columns-is-layout-constrained\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"border-style:none;border-width:0px;border-top-left-radius:0px;border-top-right-radius:0px;border-bottom-left-radius:0px;border-bottom-right-radius:0px;margin-bottom:var(--wp--preset--spacing--40)\"><section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard  has-ivory-000-border-color is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"   border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px;border-width:10px;\">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-000-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<figure class=\"wp-block-image aligncenter size-full has-custom-border\"><img loading=\"lazy\" decoding=\"async\" width=\"934\" height=\"626\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-diet-consuption-hyperphagia.webp\" alt=\"Line graph showing daily diet consumption over time in rodents during baseline, morphine dependence, and withdrawal, highlighting increased food intake (hyperphagia) during morphine withdrawal compared with vehicle controls.\" class=\"wp-image-16692\" style=\"border-style:none;border-width:0px;border-top-left-radius:0px;border-top-right-radius:0px;border-bottom-left-radius:0px;border-bottom-right-radius:0px;object-fit:cover\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-diet-consuption-hyperphagia.webp 934w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-diet-consuption-hyperphagia-300x201.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-diet-consuption-hyperphagia-768x515.webp 768w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-diet-consuption-hyperphagia-537x360.webp 537w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-diet-consuption-hyperphagia-640x429.webp 640w\" sizes=\"(max-width: 934px) 100vw, 934px\"><\/figure>\n<\/div>\n\n<\/div>\n\t\t\n\t        <\/section>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\"><section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard  has-ivory-000-border-color is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"   border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px;border-width:10px;\">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-000-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<figure class=\"wp-block-image aligncenter size-full has-custom-border\"><img loading=\"lazy\" decoding=\"async\" width=\"647\" height=\"438\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-water-consuption-hyperdipsia.webp\" alt=\"Line graph showing daily water consumption over time in rodents during baseline, morphine dependence, and withdrawal, highlighting increased water intake (hyperdipsia) during morphine withdrawal compared with vehicle controls.\" class=\"wp-image-16691\" style=\"border-style:none;border-width:0px;border-top-left-radius:0px;border-top-right-radius:0px;border-bottom-left-radius:0px;border-bottom-right-radius:0px;object-fit:cover\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-water-consuption-hyperdipsia.webp 647w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-water-consuption-hyperdipsia-300x203.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-water-consuption-hyperdipsia-532x360.webp 532w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-daily-water-consuption-hyperdipsia-640x433.webp 640w\" sizes=\"(max-width: 647px) 100vw, 647px\"><\/figure>\n<\/div>\n\n<\/div>\n\t\t\n\t        <\/section>\n<\/div>\n<\/div>\n\n\n\n<p class=\"has-text-align-center has-text-sm-font-size\"><em><em><em><em>Daily diet and water consumption during baseline (vehicle treatment), induction of dependence (vehicle or morphine treatment) and withdrawal (vehicle or methadone treatment). Red circles highlight morphine withdrawal induced hyperphagia and hyperdipsia. *p&lt;0.05, **p&lt;0.01, ***p&lt;0.001 versus vehicle.<\/em><\/em><\/em><\/em><\/p>\n\n<\/div>\n\t\t\n\t        <\/section>\n\n\n\n<p style=\"padding-top:var(--wp--preset--spacing--40)\">In contrast, rats that were administered methadone during the withdrawal phase did not exhibit hyperphagia or hyperdipsia and behaviors linked to poor health and stress were reduced or absent. Similarly to methadone in the clinic, adverse effects such as decreased respiration were present. These effects are mediated in the clinic by starting treatment at a low dose and slowly increasing to a therapeutic dose.<\/p>\n\n\n\n<p>Overall, these results confirm that methadone reduces opioid withdrawal symptoms in rats similar to the effect seen in humans.<\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\" style=\"border-width:10px;border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:25%\"><\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-top is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:50%\"><section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard  has-ivory-000-border-color is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"   border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px;border-width:10px;\">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-000-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<figure class=\"wp-block-image aligncenter size-full has-custom-border\" style=\"margin-bottom:var(--wp--preset--spacing--40)\"><img loading=\"lazy\" decoding=\"async\" width=\"848\" height=\"915\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-behavioral-observations-heatmap.webp\" alt=\"Heatmap table summarising behavioural observations in rodents during morphine dependence, morphine withdrawal, and methadone treatment, showing the severity of behaviours such as Straub tail, increased body tone, irritability, and withdrawal signs compared with vehicle controls.\" class=\"wp-image-16693\" style=\"border-style:none;border-width:0px;border-top-left-radius:0px;border-top-right-radius:0px;border-bottom-left-radius:0px;border-bottom-right-radius:0px\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-behavioral-observations-heatmap.webp 848w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-behavioral-observations-heatmap-278x300.webp 278w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-behavioral-observations-heatmap-768x829.webp 768w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-behavioral-observations-heatmap-334x360.webp 334w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/04\/morphine-withdrawal-behavioral-observations-heatmap-593x640.webp 593w\" sizes=\"(max-width: 848px) 100vw, 848px\"><\/figure>\n\n\n\n<p class=\"has-text-align-center has-text-sm-font-size\"><em><em><em><em>Behavioral observations during morphine dependence (morphine 30 mg\/kg, twice daily) or morphine withdrawal, or morphine withdrawal with methadone treatment. Comparisons against vehicle by Wilcoxon Rank Sum test (all p&lt;0.05-0.001). Mean score: +&lt;0.025, ++0.25-0.49, +++0.5-0.74, ++++&gt;0.75.<\/em><\/em><\/em><\/em><\/p>\n<\/div>\n\n<\/div>\n\t\t\n\t        <\/section>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:25%\"><\/div>\n<\/div>\n\n\n<section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"  padding-bottom:var(--wp--preset--spacing--80);padding-top:var(--wp--preset--spacing--50); \">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-300-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<p><\/p>\n\n\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" style=\"padding-bottom:var(--wp--preset--spacing--30)\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\"><div x-data=\"tabButtons\" x-init=\"initTabButtons('alderley-park')\" class=\"TabButtons aligncenter wp-elements-99a560a628086d67fb5f46c0753fce5e\">\n\n            \n            <div class=\"TabButtons__inner p-1 inline-flex w-fit space-x-1 rounded-full justify-between items-center overflow-auto no-scrollbar has--font-size\" style=\"background-color: #ffffff;\">\n                                                                        <button type=\"button\" name=\"alderley-park\" x-show=\"activeTab == 'alderley-park'\" x-cloak class=\"TabButtons__button w-auto px-6 h-9 font-normal font-body leading-none rounded-full pointer-events-none whitespace-nowrap transition-colors ease-in-out\" style=\"background-color:#f9f2e8; \">\n                                <span>Up Next<\/span>\n                        <\/button>\n                        <button type=\"button\" x-on:click=\"showTab('alderley-park');\" x-show=\"activeTab != 'alderley-park'\" class=\"TabButtons__button w-auto px-6 h-9 font-normal font-body leading-none rounded-full whitespace-nowrap transition-colors ease-in-out  \" style=\" color: #002b46 \">\n                            <span>Up Next<\/span>\n                        <\/button>\n                                                                                <button type=\"button\" name=\"nottingham\" x-show=\"activeTab == 'nottingham'\" x-cloak class=\"TabButtons__button w-auto px-6 h-9 font-normal font-body leading-none rounded-full pointer-events-none whitespace-nowrap transition-colors ease-in-out\" style=\"background-color:#f9f2e8; \">\n                                <span>Addiction Research Series<\/span>\n                        <\/button>\n                        <button type=\"button\" x-on:click=\"showTab('nottingham');\" x-show=\"activeTab != 'nottingham'\" class=\"TabButtons__button w-auto px-6 h-9 font-normal font-body leading-none rounded-full whitespace-nowrap transition-colors ease-in-out  \" style=\" color: #002b46 \">\n                            <span>Addiction Research Series<\/span>\n                        <\/button>\n                                                                                <button type=\"button\" name=\"glasgow\" x-show=\"activeTab == 'glasgow'\" x-cloak class=\"TabButtons__button w-auto px-6 h-9 font-normal font-body leading-none rounded-full pointer-events-none whitespace-nowrap transition-colors ease-in-out\" style=\"background-color:#f9f2e8; \">\n                                <span>CNS &amp; Pain Models<\/span>\n                        <\/button>\n                        <button type=\"button\" x-on:click=\"showTab('glasgow');\" x-show=\"activeTab != 'glasgow'\" class=\"TabButtons__button w-auto px-6 h-9 font-normal font-body leading-none rounded-full whitespace-nowrap transition-colors ease-in-out  \" style=\" color: #002b46 \">\n                            <span>CNS &amp; Pain Models<\/span>\n                        <\/button>\n                                                        <\/div>\n    \n            <\/div>\n<\/div>\n\n\n<div class=\"TabItem\" x-data=\"TabItem\" x-init=\"initTabItem('nottingham')\">\n\t        \n    \t\t<div x-show=\"showTabItem\" x-transition:enter=\"transition ease-out duration-400 delay-200\" x-transition:enter-start=\"opacity-0\" x-transition:enter-end=\"opacity-100\" x-cloak>\n\n\t\t\t<div class=\"acf-innerblocks-container\">\n<section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"  padding-left:var(--wp--preset--spacing--50);padding-right:var(--wp--preset--spacing--50);padding-top:var(--wp--preset--spacing--50);padding-bottom:var(--wp--preset--spacing--50); border-color:#FFFFFF;border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px;border-width:10px;\">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-000-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<h2 class=\"wp-block-heading has-text-align-center has-text-4-xl-font-size\" style=\"padding-bottom:var(--wp--preset--spacing--30)\">Explore our addiction research models<\/h2>\n<\/div>\n\n\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<p class=\"has-content-primary-color has-text-color has-link-color has-text-base-font-size wp-elements-c80736ed41bf630ccf950d57dc238f05\">This article forms part of a four-part series exploring substance use disorders through the <strong>three-phase model of addiction<\/strong> and the <strong>preclinical behavioral pharmacology models<\/strong> used to support drug discovery.<\/p>\n\n\n\n<p>Together, these articles examine how addiction develops, why it is so persistent, and how validated <em>in vivo <\/em>models are used to assess new therapeutic approaches. <\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li class=\"has-blue-300-color has-text-color has-link-color wp-elements-201e76e868c531f17048369579fe37ca\"><a href=\"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/drug-addiction-a-public-health-issue\/\">Drug Addiction: A Public Health Issue That Refuses to go Away<\/a><\/li>\n<\/ul>\n\n\n\n<p>An introduction to substance use disorders, the three-phase addiction model, and the role of behavioral pharmacology.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li class=\"has-blue-300-color has-text-color has-link-color wp-elements-1ddf9a6c5f83f18ef832301ca2b578c4\"><a href=\"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/substance-use-intoxication-binge-insights-from-preclinical-models\/\">Preclinical Models of Substance Use Intoxication (Binge)<\/a><\/li>\n<\/ul>\n\n\n\n<p>How reward-driven drug use and escalation are modelled <em>in vivo<\/em>. <\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Preclinical Models of Substance Use Withdrawal<\/li>\n<\/ul>\n\n\n\n<p>Assessing dependence, withdrawal symptoms and maintenance therapies. <\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li class=\"has-blue-300-color has-text-color has-link-color wp-elements-976994f562837ec1b79d0bc43a02d66f\"><a href=\"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/preclinical-models-of-craving-and-relapse\/\">Preclinical Models of Substance Use Craving<\/a><\/li>\n<\/ul>\n\n\n\n<p>Understanding cue-induced relapse using reinstatement paradigms. <\/p>\n<\/div>\n\n<\/div>\n\t\t\n\t        <\/section>\n\n<\/div>\n\t\t\t\n\t\t<\/div>\n    \n\t\t\t<\/div>\n\n\n<div class=\"TabItem\" x-data=\"TabItem\" x-init=\"initTabItem('alderley-park')\">\n\t        \n    \t\t<div x-show=\"showTabItem\" x-transition:enter=\"transition ease-out duration-400 delay-200\" x-transition:enter-start=\"opacity-0\" x-transition:enter-end=\"opacity-100\" x-cloak>\n\n\t\t\t<div class=\"acf-innerblocks-container\">\n<section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"  padding-left:var(--wp--preset--spacing--50);padding-right:var(--wp--preset--spacing--50);padding-top:var(--wp--preset--spacing--50);padding-bottom:var(--wp--preset--spacing--50); border-color:#FFFFFF;border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px;border-width:10px;\">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-000-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<h3 class=\"wp-block-heading has-text-align-center has-text-4-xl-font-size\">Continue the series<\/h3>\n\n\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<div class=\"wp-block-group has-content-primary-color has-text-color has-link-color has-text-base-font-size overflow-hidden wp-elements-847aa70bd52f8f41f48e767ad5179915 has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"hidden\" flexwrap=\"\">\n<figure class=\"wp-block-image size-large is-style-rounded-large is-style-rounded-large--1\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"606\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1-1024x606.webp\" alt=\"Sygnature Drug Discovery - Blog\" class=\"wp-image-14300\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1-1024x606.webp 1024w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1-300x178.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1-768x455.webp 768w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1-1536x909.webp 1536w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1-608x360.webp 608w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1-640x379.webp 640w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/blog-thumbnail-1.webp 1600w\" sizes=\"(max-width: 1024px) 100vw, 1024px\"><\/figure>\n<\/div>\n\n\n\n<div class=\"wp-block-group is-vertical is-layout-flex wp-container-core-group-is-layout-fe9cc265 wp-block-group-is-layout-flex\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<h3 class=\"wp-block-heading has-text-color has-link-color has-text-2-xl-font-size wp-elements-5b1bd75dd339ed08d54e3f448dc9f4cd\" style=\"color:#002b46;margin-top:var(--wp--preset--spacing--20);margin-bottom:var(--wp--preset--spacing--20)\"><strong>Next: <\/strong>Preclinical Models of Substance Use Craving<\/h3>\n\n\n\n<p class=\"has-text-color has-link-color has-text-base-font-size wp-elements-34d8474260293f4028dbff12da78bdac\" style=\"color:#001024b3;margin-bottom:var(--wp--preset--spacing--20)\">Focusing on the craving phase of addiction, this article examines how behavioral pharmacology models capture cue\u2011driven drug seeking and relapse vulnerability.<\/p>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button is-style-fill is-style-fill--2\" modaltype=\"side\"><a class=\"wp-block-button__link wp-element-button\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/preclinical-models-of-craving-and-relapse\/\">Learn more<\/a><\/div>\n<\/div>\n<\/div>\n<\/div>\n\n<\/div>\n\t\t\n\t        <\/section>\n\n<\/div>\n\t\t\t\n\t\t<\/div>\n    \n\t\t\t<\/div>\n\n\n<div class=\"TabItem\" x-data=\"TabItem\" x-init=\"initTabItem('glasgow')\">\n\t        \n    \t\t<div x-show=\"showTabItem\" x-transition:enter=\"transition ease-out duration-400 delay-200\" x-transition:enter-start=\"opacity-0\" x-transition:enter-end=\"opacity-100\" x-cloak>\n\n\t\t\t<div class=\"acf-innerblocks-container\">\n<section class=\"Pegasus__Container w-full   relative h-fit  text-content-dark mobile-stacking-standard is-layout-flow wp-block-pegasus-container-is-layout-flow\" style=\"  padding-left:var(--wp--preset--spacing--50);padding-right:var(--wp--preset--spacing--50);padding-top:var(--wp--preset--spacing--50);padding-bottom:var(--wp--preset--spacing--50); border-color:#FFFFFF;border-top-left-radius:25px;border-top-right-radius:25px;border-bottom-left-radius:25px;border-bottom-right-radius:25px;border-width:10px;\">\n\t        \n\t\n\t\t\t\t\t\t\n\t\t        \t\t\n\t\t\t\t\t\t\t<div class=\"row-background absolute w-full bottom-0 left-0 z-0 h-full has-ivory-000-background-color\" style=\"\">\n<\/div>\n\t\t\t\t\t\n\t\t\t<div class=\"inner relative h-full is-flex-layout flex flex-col justify-start  w-full\">\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<h2 class=\"wp-block-heading has-text-align-center has-text-4-xl-font-size\">CNS &amp; Pain Models<\/h2>\n\n\n\n<div class=\"wp-block-group has-content-primary-color has-text-color has-link-color has-text-base-font-size overflow-hidden wp-elements-9ed9bb46cc2365c6813e51baec3b5457 has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"hidden\" flexwrap=\"\">\n<figure class=\"wp-block-image size-large is-style-rounded-large is-style-rounded-large--3\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"575\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration-1024x575.webp\" alt=\"diagram illustration of interconnected neurons representing central nervous system drug discovery, highlighting neural pathways and synaptic connections for therapeutic research.\" class=\"wp-image-7745\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration-1024x575.webp 1024w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration-300x169.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration-768x432.webp 768w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration-1536x863.webp 1536w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration-1920x1080.webp 1920w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration-640x360.webp 640w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/cns-drug-discovery-neural-network-illustration.webp 2000w\" sizes=\"(max-width: 1024px) 100vw, 1024px\"><\/figure>\n<\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained\" allowchildrentofillwidth=\"\" overflow=\"\" flexwrap=\"\">\n<p class=\"has-content-primary-color has-text-color has-link-color has-text-base-font-size wp-elements-f58785d528a8df706bde7b033c502336\" style=\"padding-top:var(--wp--preset--spacing--20)\">Addiction research depends on validated <em>in vivo <\/em>behavioral pharmacology models to assess reward, reinforcement, dependence and relapse-relevant behaviors. <\/p>\n\n\n\n<p>These approaches form part of Sygnature Discovery\u2019s <strong>CNS &amp; pain <em>in vivo <\/em>pharmacology capabilities, <\/strong>supporting translational neuroscience and substance use disorder drug discovery from early research through to clinical decision-making. <\/p>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button is-style-fill is-style-fill--4\" modaltype=\"\"><a class=\"wp-block-button__link wp-element-button\" href=\"https:\/\/www.sygnaturediscovery.com\/in-vivo-pharmacology\/cns-and-pain-models\/\">Explore our CNS &amp; Pain Model Solutions <\/a><\/div>\n<\/div>\n<\/div>\n\n<\/div>\n\t\t\n\t        <\/section>\n\n<\/div>\n\t\t\t\n\t\t<\/div>\n    \n\t\t\t<\/div>\n\n<\/div>\n\t\t\n\t        <\/section>\n","protected":false},"excerpt":{"rendered":"<p>Focusing on the withdrawal phase of addiction, this article examines how behavioral pharmacology models assess drug dependence and therapeutic intervention in preclinical studies.<\/p>\n","protected":false},"featured_media":0,"template":"","category":[1412,816],"class_list":["post-16868","blog","type-blog","status-publish","hentry","category-cns-pain-models","category-pharmacologie-in-vivo"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Substance Use Withdrawal: Preclinical Models &amp; Treatment<\/title>\n<meta name=\"description\" content=\"Learn how preclinical withdrawal models are designed and applied, including an opioid withdrawal case study validated with methadone.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/preclinical-models-of-substance-use-withdrawal\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Substance Use Withdrawal: Preclinical Models &amp; Treatment\" \/>\n<meta property=\"og:description\" content=\"Learn how preclinical withdrawal models are designed and applied, including an opioid withdrawal case study validated with methadone.\" \/>\n<meta property=\"og:url\" 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