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Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms

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Abstract

Rationale

Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated.

Objective

In this study, we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats.

Results

The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic, or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909, and the noradrenaline reuptake inhibitor atomoxetine.

Conclusions

Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline, and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon.

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Acknowledgments

Supported by the National Institute on Drug Abuse Grant R01 DA022628 (L.J.M.J.V.), Netherlands Organization for Scientific Research (NWO) Veni grant 91611052 (V.T.), and Marie Curie Career Reintegration Grant PCIG09-GA-2011-293589 (V.T.).

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Authors and Affiliations

  1. Department of Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM, Utrecht, The Netherlands

    E. J. Marijke Achterberg & Louk J. M. J. Vanderschuren

  2. Department of Neuroscience and Pharmacology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    Viviana Trezza & Louk J. M. J. Vanderschuren

  3. Department of Sciences, Section of Biomedical Sciences and Technologies, University “Roma Tre”, Viale G. Marconi 446, 00146, Rome, Italy

    Viviana Trezza

  4. Department of Psychology, Gettysburg College, Gettysburg, PA, USA

    Stephen M. Siviy

  5. Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands

    Laurens Schrama & Anton N. M. Schoffelmeer

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  1. E. J. Marijke Achterberg
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  2. Viviana Trezza
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  3. Stephen M. Siviy
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  4. Laurens Schrama
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  5. Anton N. M. Schoffelmeer
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  6. Louk J. M. J. Vanderschuren
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Corresponding authors

Correspondence to Viviana Trezza or Louk J. M. J. Vanderschuren.

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Marijke Achterberg and Viviana Trezza contributed equally to the study.

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Achterberg, E.J.M., Trezza, V., Siviy, S.M. et al. Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms. Psychopharmacology 231, 1503–1515 (2014). https://doi.org/10.1007/s00213-013-3272-9

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  • DOI: https://doi.org/10.1007/s00213-013-3272-9

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