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

Hirohito Esaki, Yuki Sasaki, Naoya Nishitani, Hikari Kamada, Satoko Mukai, Yoshitaka Ohshima, Sao Nakada, Xiyan Ni, Satoshi Deyama, Katsuyuki Kaneda

European Journal of Pharmacology March 10, 2023 DOI: 10.1016/j.ejphar.2023.175653 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Male ICR mice
Interventions MDMA (S)-citalopram WAY100635
Measures social approach test
Topics MDMA Serotonin
Keywords Animals Mice, inbred icr N-methyl-3,4-methylenedioxyamphetamine Receptor, serotonin, 5-ht1a Serotonin antagonists Male Basolateral nuclear complex Sert Basolateral amygdala Sociability 5-ht1a receptors
Key findings MDMA-induced prosocial effects in male ICR mice were suppressed by the 5-HT1A receptor antagonist WAY100635, but not by (S)-citalopram or antagonists of 5-HT1B, 5-HT2A, 5-HT2C, or 5-HT4 receptors. Local infusion of WAY100635 into the basolateral amygdala, but not the medial prefrontal cortex, suppressed the effect, and intra-amygdala MDMA increased sociability. The authors suggest MDMA acts through 5-HT1A receptors in the basolateral amygdala.

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-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.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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MDMA Serotonin