Serotonin (1A) receptor involvement in acute 3,4- methylenedioxymethamphetamine (MDMA) facilitation of social interaction in the rat

The current study assessed whether various co-administered serotonin (5-HT) receptor antagonists could prevent some of the acute behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in rats. In the social interaction test, MDMA (5 mg/kg) significantly increased the duration of total social interaction between two conspecifics meeting for the first time. Microanalysis showed that MDMA increased adjacent lying and approach behaviours while reducing anogenital sniffing. MDMA (5 mg/kg) also caused elements of the serotonin syndrome including low body posture and piloerection. In the emergence test, MDMA significantly increased hide time and emergence latency indicating increased anxiety-like behavior. Pretreatment with the 5HT_1A receptor antagonist, WAY 100635 (1 mg/kg), prevented MDMA-induced increases in social interaction and markers of the serotonin syndrome while the 5-HT_1B receptor antagonist GR 55562 (1 mg/kg) and 5-HT_2A receptor antagonist ketanserin (1 mg/kg) were ineffective. The 5-HT_2B/2C receptor antagonist, SB 206553 (2 mg/kg), prevented MDMA-induced prosocial effects but caused pronounced thigmotaxis (hyperactivity at the periphery of the testing chamber). The anxiogenic effect of MDMA on the emergence test was not prevented by pretreatment with any of the 5-HT receptor antagonists tested. These results indicate that prosocial effect of MDMA may involve 5-HT_1A and possibly 5-HT_2B/2C receptors. In contrast, MDMA-induced generalised anxiety, as measured by the emergence test, seems unlikely to involve the 5-HT_1A, 5-HT_1B or 5-HT_2A, 5-HT_2B or 5-HT_2C receptors.