Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms.
BACKGROUND
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.
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
EJ
Achterberg
Viviana
V
Trezza
Stephen M
SM
Siviy
Laurens
L
Schrama
Anton N M
AN
Schoffelmeer
Louk J M J
LJ
Vanderschuren
D018663:Adrenergic Agents / Q000494:pharmacology*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D005475:Flupenthixol / Q000494:pharmacology; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D010988:Play and Playthings; D011437:Propylamines / Q000494:pharmacology; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012919:Social Behavior
D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D058669:Adrenergic alpha-2 Receptor Antagonists; D000661:Amphetamine; D000069445:Atomoxetine Hydrochloride; D003042:Cocaine; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D005475:Flupenthixol; D019329:Idazoxan; D010879:Piperazines; D011437:Propylamines; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C043425:vanoxerine; C058525:2-methoxyidazoxan