Distinct neural mechanisms for the prosocial and rewarding properties of MDMA.
Sci Transl Med
; 11(522)2019 12 11.
Article
in En
| MEDLINE
| ID: mdl-31826983
ABSTRACT
The extensively abused recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA) has shown promise as an adjunct to psychotherapy for treatment-resistant psychiatric disease. It is unknown, however, whether the mechanisms underlying its prosocial therapeutic effects and abuse potential are distinct. We modeled both the prosocial and nonsocial drug reward of MDMA in mice and investigated the mechanism of these processes using brain region-specific pharmacology, transgenic manipulations, electrophysiology, and in vivo calcium imaging. We demonstrate in mice that MDMA acting at the serotonin transporter within the nucleus accumbens is necessary and sufficient for MDMA's prosocial effect. MDMA's acute rewarding properties, in contrast, require dopaminergic signaling. MDMA's prosocial effect requires 5-HT1b receptor activation and is mimicked by d-fenfluramine, a selective serotonin-releasing compound. By dissociating the mechanisms of MDMA's prosocial effects from its addictive properties, we provide evidence for a conserved neuronal pathway, which can be leveraged to develop novel therapeutics with limited abuse liability.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reward
/
Social Behavior
/
Brain
/
N-Methyl-3,4-methylenedioxyamphetamine
Aspects:
Determinantes_sociais_saude
Limits:
Animals
Language:
En
Journal:
Sci Transl Med
Journal subject:
CIENCIA
/
MEDICINA
Year:
2019
Document type:
Article
Affiliation country:
United States