Long-term changes in social interaction and reward following repeated MDMA administration to adolescent rats without accompanying serotonergic neurotoxicity.

Abstract

MDMA is a popular drug of abuse in adolescents which causes serotonergic neurotoxicity in adult but not young rodents. However, few studies have examined the long-term behavioural consequence of MDMA and it is unclear whether such changes occur in the absence of neurotoxicity. The present study examined whether treatment of young rats with MDMA produced long-term behavioural alterations without accompanying serotonergic neurotoxicity. Male Lister hooded rats ( n=36, postnatal day (PND) 39) received MDMA (7.5 mg/kg i.p., twice daily for 3 days) or saline (l ml/kg i.p.) and the acute effect on open field behaviour and body temperature was monitored. Following drug withdrawal, social interaction in pre-treatment- and weight-matched rat pairs, cortical [(3)H]paroxetine binding and hippocampal and frontal cortical serotonin and dopamine levels (PND 53, n=12) and conditioned place preference (PND 70, n=24) to cocaine (5 mg/kg IP) were analysed. MDMA elicited the expected immediate serotonin syndrome with significant hyperlocomotion, decreased rearing and hypothermia. Twelve to 29 days after the last MDMA injection social interaction was significantly attenuated (by 41%) and the sub-threshold conditioned place preference to cocaine was significantly enhanced compared with that in saline controls, although no significant side preference to cocaine occurred in the latter. MDMA pre-treatment did not alter 5-HT levels or cortical [(3)H]paroxetine binding. MDMA administration to adolescent rats reduced social interaction and enhanced the sub-threshold rewarding effect of cocaine at adulthood, despite an absence of accompanying serotonergic and dopaminergic neurotoxicity.