Role of 5-HT1A receptors in the basolateral amygdala on 3,4-methylenedioxymethamphetamine-induced prosocial effects in mice.

3,4-methylenedioxymethamphetamine (MDMA), a recreational drug, induces euphoric sensations and psychosocial effects, such as increased sociability and empathy. Serotonin, also called 5-hydroxytryptamine (5-HT), is a neurotransmitter that has been associated with MDMA-induced prosocial effects. However, the detailed neural mechanisms remain elusive. In the present study, we investigated whether 5-HT neurotransmission in the medial prefrontal cortex (mPFC) and the basolateral nucleus of amygdala (BLA) is involved in MDMA-induced prosocial effects using the social approach test in male ICR mice. Systemic administration of (S)-citalopram, a selective 5-HT transporter inhibitor, before administration of MDMA failed to suppress MDMA-induced prosocial effects. On the other hand, systemic administration of the 5-HT1A receptor antagonist WAY100635, but not 5-HT1B, 5-HT2A, 5-HT2C, or 5-HT4 receptor antagonist, significantly suppressed MDMA-induced prosocial effects. Furthermore, local administration of WAY100635 into the BLA but not into the mPFC suppressed MDMA-induced prosocial effects. Consistent with this finding, intra-BLA MDMA administration significantly increased sociability. Together, these results suggest that MDMA induces prosocial effects through the stimulation of 5-HT1A receptors in the BLA.

Differential sensitivity to detect prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA) in different social approach paradigms in mice.

A recreational drug, 3,4-methylenedioxymethamphetamine (MDMA), has prosocial effects including increased sociability, enhancement of trust feelings, and empathy. Although several methods, such as the social interaction and three chamber tests, have been used, the neural mechanisms underlying the prosocial effects have not been well understood. In the present study, based on a social approach paradigm using a single-chamber apparatus, we have developed two reproducible and simple social approach tests, SAT1 and SAT2, in ICR mice. In the SAT1, an unfamiliar mouse was set in a wire mesh cylinder cage that was placed in the center of a rectangular open field, while in the SAT2, an unfamiliar mouse was set in a wire mesh rectangular cage that was placed along a wall of a rectangular open field. Although MDMA treatment enhanced sociability in both SAT1 and SAT2, the ratio of high sociability mice was higher in the SAT2 than in the SAT1, indicating a differential sensitivity to detect the prosocial effects. Thus, we suggest that the SAT2 is a promising and suitable method to explore the neuronal mechanisms underlying the effects of MDMA.