Forced abstinence model of relapse to study pharmacological treatments of substance use disorder - PubMed (original) (raw)

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Forced abstinence model of relapse to study pharmacological treatments of substance use disorder

Carmela M Reichel et al. Curr Drug Abuse Rev. 2009 May.

Abstract

Understanding and preventing relapse to drug use is one of the most difficult challenges faced by clinicians and practitioners in the struggle to help people remain abstinent. In this paper, we review basic preclinical research on forced abstinence periods that identify the neural substrates involved and neural adaptations that occur after a drug-free period. Our attention focuses on forced abstinence after self-administration because of its promise for translational research in the development of candidate medications to reduce relapse. This model requires subjects (often rats) to initially acquire drug self-administration. However, rather than extinguishing behavior with daily drug-free sessions as in the reinstatement model of drug seeking, subjects are removed from the self-administration situation and do not receive any exposure to the drug. Notably, the integrity of the drug-taking behavior and the drug-associated cues in the drug-taking environment are preserved because they are not experienced in the absence of the drug. Research shows time dependent increases in drug-seeking following forced abstinence periods. More so, neural substrates and adaptations within the mesocorticolimbic system and the nigrostriatal system have been identified that contribute to increased drug seeking following abstinence. From a translational perspective, behavioral and pharmacological treatment of substance use disorder often starts during this initial abstinence period (either forced or voluntary). The forced abstinence model simulates some of the features of this treatment situation and thus allows for the study of potential treatments that alter relapse of drug-seeking behaviors along with the accompanying neurobiological changes.

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Figures

Figure 1

Figure 1

This figure shows active and inactive lever presses (Mean ± SEM) for rats (n= 14) trained to self-administer 0.05 mg/kg/infusion methamphetamine. Panel A depicts the acquisition of the lever press response on FR 1, 3, and 5 schedules of reinforcement and the extinction of such a response. Panel B illustrates drug-primed reinstatement tested with 0, 0.125, 0.25, and 0.5 mg/kg methamphetamine IP.

Figure 2

Figure 2

This figure shows active and inactive lever presses (Mean ± SEM) for rats (n=10) trained to self-administer 0.05 mg/kg/infusion methamphetamine. Following stable methamphetamine self-administration (last 7 days of drug access are shown), rats were given 14 days of forced abstinence followed by 2 consecutive relapse tests occurring 24 hr apart. These tests were conducted with contingent presentations of the stimulus complex on an FR5 schedule of reinforcement.

Figure 3

Figure 3

This figure is a schematic representation of the mesocorticolimbic and nigrostriatal systems that are important in relapse to cocaine seeking following abstinence. Abbreviations: NAC, nucleus accumbens; STR, striatum (caudate and putamen); GP, globus pallidus; SN, substantia nigra; VTA, ventral tegmental area.

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