Abstract
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.
Footnotes
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Send reprint requests to: Dr. Feng Chen, Department of Pharmacology, Monash University, Wellington Rd., Clayton, Victoria 3168, Australia. E-mail:Feng.Chen{at}med.monash.edu.au
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↵1 This work was part of the Ph.D. thesis of F.C. and was supported by a Monash Graduate Scholarship, Australia, and funds to A.J.L. from Australian Brewers' Foundation and the National Health and Medical Research Council, Australia. A.J.L. is an R. D. Wright Fellow of the National Health and Medical Research Council, Australia.
- Abbreviations:
- FH
- Fawn-Hooded
- GTPγS
- guanosine-5′-O-(3-thio)triphosphate
- G protein
- guanine nucleotide regulatory protein
- Gi/Go and Gs
- adenylyl cyclase inhibitory and stimulating G proteins
- Giα/Goα and Gsα
- α-subunit of Gi/Go and Gs proteins, respectively
- DAMGO
- [d-Ala2,N-MePhe4,Gly-ol5]-enkephalin
- 5-HT
- hydroxytryptamine (serotonin)
- L694,247
- 2-[5-[3-(4-methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine
- 8-OH-DPAT
- 8-hydroxy-2-dipropylaminotetralin
- Received October 7, 1999.
- Accepted December 7, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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