Results also point to the N/OFQ system as another important modulator of behaviors related to stress and alcohol abuse. For example, data showed that activation of NOP receptors by N/OFQ reduces home cage ethanol drinking and operant ethanol self-administration in msP rats. N/OFQ also reduces conditioned reinstatement and stress-induced reinstatement of ethanol-seeking in rats. These effects have been well documented in msP rats. In contrast, in nonselected Wistars, N/OFQ did not alter ethanol consumption. Neurochemical and molecular data demonstrated that N/OFQ function is upregulated in the brain of msP rats compared to nonselected Wistars, with the only exception of the CeA. In this area, in fact, due to “uncoupling” of the NOP receptor from G-protein-mediated signal transduction, the system is hypofunctional. It is noteworthy that stimulation of CeA NOP receptors by administration of the exogenous ligand potently and selectively reduces alcohol self-administration in msP rats.
