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The effect of quetiapine (Seroquel™) on conditioned place preference and elevated plus maze tests in rats when administered alone and in combination with (+)-amphetamine

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Abstract

Rationale

Recent case reports describe recreational use of quetiapine and drug-seeking behaviour to obtain quetiapine, an atypical antipsychotic.

Objective

We examined the hypothesis that quetiapine (10, 20 or 40 mg/kg) alone or co-administered with (+)-amphetamine (0.25, 0.5, 0.75 or 2.0 mg/kg) will affect reward and/or decrease anxiety in rats, as measured by conditioned place preference (CPP) and elevated plus maze (EPM) test, respectively.

Results

Quetiapine (20 mg/kg) produced greater open arm time and entries in the EPM test compared to 10 and 40 mg/kg, and quetiapine (10 mg/kg) significantly increased open arm entries and time when co-administered with (+)-amphetamine (0.5 mg/kg) compared to (+)-amphetamine (0.5 mg/kg) alone, suggesting decreased anxiety. Quetiapine (10, 20 or 40 mg/kg) produced no CPP when administered alone; the lowest dose of quetiapine (10 mg/kg) reduced CPP produced by a low dose of (+)-amphetamine (0.25 mg/kg), but had no significant effect on CPP produced by a higher dose (0.5 mg/kg).

Discussion

The quetiapine-induced anxiolytic effect in the EPM might explain why humans are misusing quetiapine and combining it with (+)-amphetamine. It is possible that humans experience an anxiolytic effect of the combined drugs and relatively unaltered rewarding effects of (+)-amphetamine. The results shed some light on the question of why humans are abusing and misusing quetiapine, despite its dopamine (DA) D2 receptor antagonism; it will be the task of future studies to identify the pharmacological mechanism mediating this behaviour.

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Acknowledgments

The authors thank Tyson Baker and Josh Lister of the Department of Psychology, Queen’s University for their assistance in this study. Prof Richard J Beninger was funded by a grant from the Natural Sciences and Engineering Research Council of Canada.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Psychology, Queen’s University, Kingston, Ontario, Canada, K7L 3N6

    Angela E. McLelland & Richard J. Beninger

  2. Department of Psychiatry, Queen’s University, Kingston, Ontario, Canada, K7L 3N6

    Richard J. Beninger

  3. Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia, 6009

    Angela E. McLelland & Mathew T. Martin-Iverson

Authors
  1. Angela E. McLelland
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  2. Mathew T. Martin-Iverson
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  3. Richard J. Beninger
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Correspondence to Mathew T. Martin-Iverson.

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McLelland, A.E., Martin-Iverson, M.T. & Beninger, R.J. The effect of quetiapine (Seroquel™) on conditioned place preference and elevated plus maze tests in rats when administered alone and in combination with (+)-amphetamine. Psychopharmacology 231, 4349–4359 (2014). https://doi.org/10.1007/s00213-014-3578-2

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  • DOI: https://doi.org/10.1007/s00213-014-3578-2

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