Effect of the Novel Positive Allosteric Modulator of Metabotropic Glutamate Receptor 2 AZD8529 on Incubation of Methamphetamine Craving After Prolonged Voluntary Abstinence in a Rat Model

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• 作者：Daniele Caprioli^a ; ^{daniele.caprioli@nih.gov" class="auth_mail" title="E-mail the corresponding author} ; Marco Venniro^a ; ^b ; Tamara Zeric^a ; Xuan Li^a ; Sweta Adhikary^a ; Rajtarun Madangopal^a ; Nathan J. Marchant^a ; ^c ; Federica Lucantonio^d ; Geoffrey Schoenbaum^a ; Jennifer M. Bossert^a ; Yavin Shaham^a
• 关键词：Abstinence ; Addiction models ; Discrete choice ; Extended access ; Glutamate ; Incubation of drug craving ; mGluR2/3 ; Palatable food ; Positive allosteric modulator ; Psychostimulants ; Relapse ; Self-administration
• 刊名：Biological Psychiatry
• 出版年：2015
• 出版时间：1 October 2015
• 年：2015
• 卷：78
• 期：7
• 页码：463-473
• 全文大小：401 K

文摘

Cue-induced methamphetamine craving increases after prolonged forced (experimenter-imposed) abstinence from the drug (incubation of methamphetamine craving). Here, we determined whether this incubation phenomenon would occur under conditions that promote voluntary (self-imposed) abstinence. We also determined the effect of the novel metabotropic glutamate receptor 2 positive allosteric modulator, AZD8529, on incubation of methamphetamine craving after forced or voluntary abstinence.

c_2">Methods

We trained rats to self-administer palatable food (6 sessions) and then to self-administer methamphetamine under two conditions: 12 sessions (9 hours/day) or 50 sessions (3 hours/day). We then assessed cue-induced methamphetamine seeking in extinction tests after 1 or 21 abstinence days. Between tests, the rats underwent either forced abstinence (no access to the food- or drug-paired levers) or voluntary abstinence (achieved via a discrete choice procedure between methamphetamine and palatable food; 20 trials per day) for 19 days. We also determined the effect of subcutaneous injections of AZD8529 (20 and 40 mg/kg) on cue-induced methamphetamine seeking 1 day or 21 days after forced or voluntary abstinence.

c_3">Results

Under both training and abstinence conditions, cue-induced methamphetamine seeking in the extinction tests was higher after 21 abstinence days than after 1 day (incubation of methamphetamine craving). AZD8529 decreased cue-induced methamphetamine seeking on day 21 but not day 1 of forced or voluntary abstinence.

c_4">Conclusions

We introduce a novel animal model to study incubation of drug craving and cue-induced drug seeking after prolonged voluntary abstinence, mimicking the human condition of relapse after successful contingency management treatment. Our data suggest that positive allosteric modulators of metabotropic glutamate receptor 2 should be considered for relapse prevention.