RT Journal Article
SR Electronic
T1 Effect of Chronic Ethanol and Withdrawal on the μ-Opioid Receptor- and 5-Hydroxytryptamine<sub>1A</sub> Receptor-Stimulated Binding of [<sup>35</sup>S]Guanosine-5′-<em>O</em>-(3-thio)triphosphate in the Fawn-Hooded Rat Brain: A Quantitative Autoradiography Study
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 159
OP 165
VO 293
IS 1
A1 Feng Chen
A1 Andrew J. Lawrence
YR 2000
UL http://jpet.aspetjournals.org/content/293/1/159.abstract
AB Previous studies have shown that chronic ethanol influences the density of central μ-opioid receptors and serotonin1A(5-hydroxytryptamine1A) receptors. To determine whether the functional coupling of these two receptors to G proteins in the rat brain, particularly in mesocorticolimbic regions, is affected by ethanol, receptor-mediated [35S]guanosine-5′-O-(3-thio)-triphosphate ([35S]GTPγS) binding stimulated by [d-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) or L694,247 was used. By quantitative autoradiography, receptor-mediated [35S]GTPγS binding activated by the two agonists was mapped throughout brain sections at the level of the nucleus accumbens and hippocampus from groups of alcohol-preferring Fawn-Hooded (FH) rats after different ethanol consumption paradigms. Significant DAMGO (μ-opioid receptor agonist)-stimulated binding of [35S]GTPγS was obtained in the striatum, nucleus accumbens, and lateral septum, whereas L694,247 (5-hydroxytryptamine1A/1B/1D receptor agonist)-stimulated binding of [35S]GTPγS was observed in the lateral septum, amygdala, and cingulate cortex. Chronic ethanol self-administration significantly reduced DAMGO-stimulated [35S]GTPγS binding in the nucleus accumbens (−19%), lateral septum (−15%), and striatum (−23%), which recovered toward control levels after ethanol withdrawal. However, chronic ethanol, as well as ethanol withdrawal, failed to produce any significant alteration in L694,247-stimulated [35S]GTPγS binding in all tested brain regions. The region-specific and receptor-specific alteration of agonist-stimulated [35S]GTPγS binding suggests that the change of functional coupling of μ-opioid receptors to G proteins induced by chronic ethanol drinking may have a pathophysiological role in the consequences of ethanol consumption. The American Society for Pharmacology and Experimental Therapeutics