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Effects of quetiapine treatment on cocaine self-administration and behavioral indices of sleep in adult rhesus monkeys

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Abstract

Rationale

Clinical literature suggests a link between substance abuse and sleep disturbances. Quetiapine, an atypical antipsychotic, has shown efficacy in treating sleep disturbances, with clinical studies showing promise for quetiapine as a treatment for cocaine abuse.

Objective

The goal of this study was to examine the effects of quetiapine on cocaine self-administration and behavioral indices of sleep in monkeys.

Methods

Seven adult male rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a choice paradigm of food (1.0-g pellets) and cocaine (0.003–0.3 mg/kg per injection) presentation. First, monkeys received acute pretreatment (45 min) with quetiapine (25–75 mg, p.o.) prior to choice sessions; three cocaine doses were studied in combination with quetiapine. Next, the effect of chronic (14–16 days) quetiapine treatment (25–250 mg, p.o., BID) was examined in combination with the lowest preferred cocaine dose (≥80 % cocaine choice). Behavioral indices of sleep, based on activity measures obtained during lights-out, were recorded throughout the study.

Results

Acute quetiapine decreased cocaine choice in four of the seven monkeys. Chronic quetiapine treatment resulted in initial decreases in cocaine choice, but tolerance developed to these effects. Acute doses of quetiapine did not improve sleep efficiency the following night nor did chronic quetiapine. The first night after discontinuing quetiapine treatment resulted in significant decreases in sleep efficiency and increases in nighttime activity.

Conclusions

These findings do not offer support for the use of quetiapine as a monotherapy for treatment of cocaine abuse nor as an adjunct therapy to treat sleep disturbances associated with stimulant abuse.

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Acknowledgments

We would like to thank Tonya Calhoun and Michael Coller for excellent technical assistance and Dr. Paul Czoty for comments on an earlier version of this manuscript. This research was supported by the National Institute on Drug Abuse grants DA025120 and DA012460.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA

    Robert E. Brutcher & Michael A. Nader

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  1. Robert E. Brutcher
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  2. Michael A. Nader
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Correspondence to Michael A. Nader.

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Brutcher, R.E., Nader, M.A. Effects of quetiapine treatment on cocaine self-administration and behavioral indices of sleep in adult rhesus monkeys. Psychopharmacology 232, 411–420 (2015). https://doi.org/10.1007/s00213-014-3672-5

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  • DOI: https://doi.org/10.1007/s00213-014-3672-5

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