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

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.