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Incubation of Methamphetamine but not Heroin Craving After Voluntary Abstinence in Male and Female Rats.

ABSTRACT: We recently introduced an animal model of incubation of methamphetamine craving after choice-based voluntary abstinence in male rats. Here we studied the generality of this phenomenon to (1) female rats, and (2) male and female rats with a history of heroin self-administration. We first trained rats to self-administer palatable food pellets for 6 days (6?h per day) for either methamphetamine (0.1?mg/kg/infusion) or heroin (0.1?mg/kg/infusion) for 12 days (6?h/day). We then assessed relapse to drug seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent either voluntary abstinence (achieved via a discrete choice procedure between drug and palatable food; 20 trials/day) or home-cage forced abstinence. We found no sex differences in methamphetamine self-administration or in the strong preference for the palatable food over methamphetamine during the choice-based voluntary abstinence. In both sexes, methamphetamine seeking in the relapse tests was higher after 21 days of either voluntary or forced abstinence than after 1 day (incubation of methamphetamine craving). We also found no sex differences in heroin self-administration or the strong preference for the palatable food over heroin during the choice-based voluntary abstinence. However, male and female rats with a history of heroin self-administration showed incubation of heroin craving after forced but not voluntary abstinence. Our results show that incubation of methamphetamine craving after voluntary abstinence generalizes to female rats. Unexpectedly, prolonged voluntary abstinence prevented the emergence of incubation of heroin craving in both sexes.

SUBMITTER: Venniro M

PROVIDER: S-EPMC5506794 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Incubation of Methamphetamine but not Heroin Craving After Voluntary Abstinence in Male and Female Rats.

Venniro Marco M Zhang Michelle M Shaham Yavin Y Caprioli Daniele D

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20161227 5

We recently introduced an animal model of incubation of methamphetamine craving after choice-based voluntary abstinence in male rats. Here we studied the generality of this phenomenon to (1) female rats, and (2) male and female rats with a history of heroin self-administration. We first trained rats to self-administer palatable food pellets for 6 days (6 h per day) for either methamphetamine (0.1 mg/kg/infusion) or heroin (0.1 mg/kg/infusion) for 12 days (6 h/day). We then assessed relapse to dr ...[more]

PMID: 28025975

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Project description:We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d. We used in situ hybridization to measure the colabeling of the activity marker Fos with Drd1 and Drd2 in DMS and DLS after the tests. Based on the in situ hybridization colabeling results, we tested the causal role of DMS D1 and D2 family receptors, and DMS neuronal ensembles in "incubated" methamphetamine seeking, using selective dopamine receptor antagonists (SCH39166 or raclopride) and the Daun02 chemogenetic inactivation procedure, respectively. Methamphetamine seeking was higher after 21 d of voluntary abstinence than after 1 d (incubation of methamphetamine craving). The incubated response was associated with increased Fos expression in DMS but not in DLS; Fos was colabeled with both Drd1 and Drd2 DMS injections of SCH39166 or raclopride selectively decreased methamphetamine seeking after 21 abstinence days. In Fos-lacZ transgenic rats, selective inactivation of relapse test-activated Fos neurons in DMS on abstinence day 18 decreased incubated methamphetamine seeking on day 21. Results demonstrate a role of DMS dopamine D1 and D2 receptors in the incubation of methamphetamine craving after voluntary abstinence and that DMS neuronal ensembles mediate this incubation. SIGNIFICANCE STATEMENT:In human addicts, abstinence is often self-imposed and relapse can be triggered by exposure to drug-associated cues that induce drug craving. We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we used classical pharmacology, in situ hybridization, immunohistochemistry, and the Daun02 inactivation procedure to demonstrate a critical role of dorsomedial striatum neuronal ensembles in this new form of incubation of drug craving.

Dataset Information

Incubation of Methamphetamine but not Heroin Craving After Voluntary Abstinence in Male and Female Rats.

Publications

Incubation of Methamphetamine but not Heroin Craving After Voluntary Abstinence in Male and Female Rats.

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