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Psychopharmacology (Berl). 2013 Mar;226(1):45-51. doi: 10.1007/s00213-012-2882-y. Epub 2012 Sep 26.

Exaggerated cue-induced reinstatement of cocaine seeking but not incubation of cocaine craving in a developmental rat model of schizophrenia.

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  • 1Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St, HSFII, Room S251, Baltimore, MD 21201, USA.

Abstract

RATIONALE:

Patients with schizophrenia exhibit high comorbidity for substance abuse, but the biological underpinnings of this dual-diagnosis condition are still unclear. Previous studies have shown that rats with a neonatal ventral hippocampal lesion (NVHL), a widely used developmental animal model of schizophrenia, exhibit increased cocaine and methamphetamine self-administration and cocaine-induced reinstatement.

OBJECTIVE:

Here, we assessed whether a NVHL would also potentiate cue-induced reinstatement of cocaine seeking and the time-dependent increases in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving) in adult rats.

METHODS:

Rats were trained to self-administer cocaine (3 or 6 h/day with 0.75 mg kg(-1) infusion(-1) paired with a tone-light cue) for 10 days, followed by extinction training (3 h/day) and cue-induced reinstatement of cocaine seeking. Other rats were tested for incubation of cocaine craving, assessed in extinction tests 1 and 30 days after the last self-administration session.

RESULTS:

Although there was no significant difference in cocaine intake between NVHL and sham controls, NVHL rats took significantly longer to reach an a priori set extinction criterion and exhibited enhanced cue-induced reinstatement. However, while cue-induced cocaine seeking was higher after 30 days than after 1 day of withdrawal (incubation of cocaine craving), the NVHL had no effect on this incubation.

CONCLUSION:

These data confirm previous reports on enhanced resistance to extinction after NVHL and demonstrate that NVHL rats exhibit enhanced cue-induced reinstatement of cocaine seeking after extinction, a measure of drug relapse.

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