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Biol Psychiatry. 2015 Oct 1;78(7):463-73. doi: 10.1016/j.biopsych.2015.02.018. Epub 2015 Feb 23.

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.

Author information

1
Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland. Electronic address: daniele.caprioli@nih.gov.
2
Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland; Neuropsychopharmacology Laboratory, Section of Pharmacology, Department Public Health and Community Medicine, University of Verona, Verona, Italy.
3
Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland.
4
Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland; Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville, Victoria, Australia.
5
The Solomon H. Snyder Department of Neuroscience, Brain Science Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

BACKGROUND:

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.

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.

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.

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.

KEYWORDS:

Abstinence; Addiction models; Discrete choice; Extended access; Glutamate; Incubation of drug craving; Palatable food; Positive allosteric modulator; Psychostimulants; Relapse; Self-administration; mGluR2/3

PMID:
25861699
PMCID:
PMC4546920
DOI:
10.1016/j.biopsych.2015.02.018
[Indexed for MEDLINE]
Free PMC Article

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