Regional Influence of Cannabinoid CB1 Receptors in the Regulation of Ethanol Self-Administration by Wistar Rats.

Abstract

Substantial evidence suggests a facilitatory influence of cannabinoid CB₁ receptors in the modulation of ethanol consumption by rodents. Studies performed in rats selectively bred for high alcohol preference point to an involvement of CB₁ receptors in the nucleus accumbens (NAC), ventral tegmental area (VTA) and medial prefrontal cortex (mPFC) in the modulation ethanol self-administration. However, the neural mechanisms through which CB₁ receptors regulate ethanol intake in out-bred Wistar rats have not been investigated. The present study evaluated alterations in ethanol self-administration induced by localized infusions of the CB₁ receptor antagonist SR141716A (0, 1 and 3 μg/side) into the NAC, anterior and posterior VTA and mPFC. Separate groups of Wistar rats were trained to operantly respond for an oral ethanol solution and prepared with bilateral injection cannulae aimed at each brain region. Results revealed significant decreases in ethanol intake following intra-NAC SR141716A administration, consistent with our prior observation of ethanol-induced increases extracellular 2-arachidonoyl glycerol (2-AG) in this brain region. We also observed a significant dose-dependent reduction in ethanol intake following SR141716A administration into the posterior, but not anterior VTA, consistent with evidence of a specific involvement of the posterior VTA in the regulation of ethanol intake. Ethanol consumption was unaltered following intra-mPFC SR141716A administration and ethanol self-administration did not induce robust changes in anandamide or 2-AG levels in mPFC microdialysates. These findings implicate an involvement of CB₁ receptors in the NAC and posterior VTA, but not anterior VTA and mPFC in the regulation of ethanol self-administration behavior by outbred Wistar rats.