Laurent Chouchana

Chronic voluntary ethanol intake hypersensitizes 5‐HT_1A autoreceptors in C57BL/6J mice

Publisher: Wiley

Date: 24-11-2008

DOI: 10.1111/J.1471-4159.2008.05733.X

Abstract: Alcoholism is a complex disorder involving, among others, the serotoninergic (5‐HT) system, mainly regulated by 5‐HT 1A autoreceptors in the dorsal raphe nucleus. 5‐HT 1A autoreceptor desensitization induced by chronic 5‐HT reuptake inactivation has been associated with a decrease in ethanol intake in mice. We investigated here whether, conversely, chronic ethanol intake could induce 5‐HT 1A autoreceptor supersensitivity, thereby contributing to the maintenance of high ethanol consumption. C57BL/6J mice were subjected to a progressive ethanol intake procedure in a free‐choice paradigm (3–10% ethanol versus tap water 21 days) and 5‐HT 1A autoreceptor functional state was assessed using different approaches. Acute administration of the 5‐HT 1A receptor agonist ipsapirone decreased the rate of tryptophan hydroxylation in striatum, and this effect was significantly larger (+75%) in mice that drank ethanol than in those drinking water. Furthermore, ethanol intake produced both an increased potency (+45%) of ipsapirone to inhibit the firing of 5‐HT neurons, and a raise (+35%) in 5‐HT 1A autoreceptor‐mediated stimulation of [ 35 S]GTP‐γ‐S binding in the dorsal raphe nucleus. These data showed that chronic voluntary ethanol intake in C57BL/6J mice induced 5‐HT 1A autoreceptor supersensitivity, at the origin of a 5‐HT neurotransmission deficit, which might be causally related to the addictive effects of ethanol intake.

Hôpital Cochin

Location: France

View Organisation

Université Paris Descartes

Location: France

View Organisation

Universite Paris-Sud Faculte De Pharmacie De Chatenay-Malabry

Location: France

View Organisation