Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

___________________________________________

Saturday, December 20, 2008

Chronic voluntary ethanol intake hypersensitizes 5-HT1A autoreceptors in C57BL/6J mice
Journal of Neurochemistry Volume 107 Issue 6, Pages 1660 - 1670

Alcoholism is a complex disorder involving, among others, the serotoninergic (5-HT) system, mainly regulated by 5-HT1A autoreceptors in the dorsal raphe nucleus. 5-HT1A 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-HT1A 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-HT1A autoreceptor functional state was assessed using different approaches.

Acute administration of the 5-HT1A 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-HT1A autoreceptor-mediated stimulation of [35S]GTP-γ-S binding in the dorsal raphe nucleus.

These data showed that chronic voluntary ethanol intake in C57BL/6J mice induced 5-HT1A autoreceptor supersensitivity, at the origin of a 5-HT neurotransmission deficit, which might be causally related to the addictive effects of ethanol intake,

Read Full Abstract

Request Reprint E-Mail: laurence.lanfumey@upmc.fr
________________________________________________