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

Abstract

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-HT_1A receptor antagonist WAY100635, but not 5-HT_1B, 5-HT_2A, 5-HT_2C, 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-HT_1A receptors in the BLA.

Keywords: 5-HT(1A) receptors; Basolateral amygdala; MDMA; SERT; Serotonin; Sociability.