Astroglial CB 1 Reveal Sex‐Specific Synaptic Effects of Amphetamine

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Mariani, Yamuna | Dalla-Tor, Tommaso | Garavaldi, Tommaso | Julio-Kalajzić, Francisca | Gisquet, Doriane | Gomez‐sotres, Paula | Cannich, Astrid | Gambino, Giuditta | Drago, Filippo | Serrat, Roman | Hurel, Imane | Chaouloff, Francis | Pouvreau, Sandrine | Bellocchio, Luigi | Marsicano, Giovanni | Covelo, Ana

Edité par CCSD ; Wiley -

International audience. ABSTRACT The Nucleus Accumbens (NAc) is a critical brain region for the effects of psychostimulant drugs. Type‐1 cannabinoid receptors (CB 1 ), the main elements of the endocannabinoid system (ECS) in the brain, participate in these effects and modulate synaptic functions in the NAc. Besides their neuronal expression, CB 1 receptors are also present in astrocytes, where they contribute to the regulation of synaptic plasticity and behavior. However, the impact of astroglial CB 1 receptors on synaptic plasticity in the NAc and on psychostimulant‐induced synaptic and behavioral effects is currently unknown. This study shows that the psychostimulant amphetamine impairs a form of astroglial CB 1 receptor‐dependent synaptic plasticity in the NAc of male, but not female mice. Consistently, locomotor effects of amphetamine require astroglial CB 1 receptors in male, but not female mice. These results, by revealing unforeseen mechanisms underlying sex‐dependent effects of amphetamine, pave the way to a better understanding of the diverse impact of psychostimulants in women and men.

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