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Brain Neurotransmitter Receptor Systems in Alcohol Treated Mice and in Mice Genetically Selected for Differences in Sensitivity to Alcohol

  • Richard A. Rabin
  • Perry B. Molinoff

Abstract

The properties of neurotransmitter receptor-effector systems were determined in C57BL/6 mice treated with 7% (v/v) ethanol and in mice selectively bred for differences in sleep time after ethanol administration. Mice treated with ethanol for 7 days and then withdrawn for 24 hours showed a decreased hypothermic response to apomorphine. There was no change in basal or dopamine-stimulated adenylate cyclase activity or in the density or affinity of the receptor for 3H-spiroperidol. A small decrease in the density of β-adrenergic receptors was observed in the cerebral cortex of alcohol-treated and withdrawn mice. This decrease was entirely due to a decrease in the density of β2-adrenergic receptors. No change was observed in cyclic AMP accumulation due to either α- or β-adrenergic receptor stimulation. Ethanol administration did result in a rapidly reversible increase in the density of muscarinic cholinergic receptors in the hippocampus and cortex.

The properties of neurotransmitter receptors were also determined in mice genetically selected for differences in sensitivity to ethanol. β-Adrenergic receptor density was lower in cortices of long-sleep (LS) mice compared to either short-sleep (SS) mice or to the heterogenous stock (HS). The lower receptor density was tissue specific since no differences in β-adrenergic receptor density were observed in the cerebellum. Cyclic AMP accumulation in response to isoproterenol was not significantly different in the cortex of the three lines of mice. The binding of 3H-spiroperidol in the striatum and of 3H-quinuclidinyl benzilate in cortex, striatum or hippocampus was the same in the three lines of mice. However, dopamine-stimulated adenylate cyclase activity was lower in striata of SS mice.

Keywords

Ethanol Administration Muscarinic Cholinergic Receptor Long Sleep Hypothermic Response Heterogeneous Stock 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Banerjee, S.P., V.K. Sharma, and J.M. Khanna, 1978, Alterations in 6-adrenergic receptor binding during ethanol withdrawal, Nature, 276: 407.PubMedCrossRefGoogle Scholar
  2. Dibner, M.D., N.R. Zahniser, B.B. Wolfe, R.A. Rabin, and P.B. Molinoff, 1980, Brain neurotransmitter receptor systems in mice genetically selected for differences in sensitivity to ethanol, Pharmacol. Biochem. Behay., in press.Google Scholar
  3. Engel, J., and S. Liljequist, 1976, The effect of long term ethanol treatment on the sensitivity of the dopamine receptors in the nucleus accumbens, Psychopharmacol., 49: 253.CrossRefGoogle Scholar
  4. Erikson, C.K., and W.L. Burnam, 1971, Cholinergic alteration of ethanol-induced sleep and death in mice, Agents Actions, 2: 8.CrossRefGoogle Scholar
  5. Erikson, C.K., and K.J. Chai, 1976, Cholinergic modification of ethanol-induced electroencephalographic synchrony in the rat, Neyropharmacol., 15: 39.CrossRefGoogle Scholar
  6. Erikson, C.K., and D.T. Graham, 1973, Alteration of cortical and reticular acetylcholine release by ethanol in vivo, J. Pharmacol. Exp. Ther., 185: 583.Google Scholar
  7. Erwin, V.G., W.D.W. Heston, G.E. McClearn, and R.A. Deitrich, 1976, Effect of hypnotics on mice genetically selected for sensitivity to ethanol, Pharmacol. Biochem. Behay., 4: 679.Google Scholar
  8. Fields, J.Z., R.D. Reisine, and H.I. Yamamura, 1977, Biochemical demonstration of dopaminergic receptors in rat and human brain using 3H-spiroperidol, Brain Res., 136: 576.CrossRefGoogle Scholar
  9. French, W.S., D.S. Palmer, M.E. Narod, P.E. Reid, and C.W. Ramey, 1975, Noradrenergic sensitivity of the cerebral cortex after chronic ethanol ingestion and withdrawal, J. Pharmacol. Exp. Ther., 194: 319.Google Scholar
  10. Goldstein, D.B., and R. Kakihana, 1975, Alcohol withdrawal reactions in mouse strains selectively bred for long or short sleep times, Life Sci., 17: 1981.Google Scholar
  11. Harden, T.K., B.B. Wolfe, J.R. Sporn, B.K. Poulos, and P.B. Molinoff, 1977, Effects of 6-hydroxydopamine on the 3-adrenergic receptor/ adenylate cyclase system in the rat cerebral cortex, J. Pharmacol. Exp. Ther., 203: 132.Google Scholar
  12. Heston, W.D.W., V.G. Erwin, S.M. Anderson, and H. Robbins, 1974, A comparison of the effects of alcohol on mice selectively bred for differences in ethanol sleep-time, Life Sci., 14: 365.PubMedCrossRefGoogle Scholar
  13. Hoffman, P.L., and B. Tabakoff, 1977, Alterations in dopamine receptor sensitivity by chronic ethanol treatment, Nature, 268: 551.PubMedCrossRefGoogle Scholar
  14. Hunt, W.A., and T.K. Dalton, 1976, Regional brain acetylcholine levels in rats acutely treated with ethanol or rendered ethanol-dependent, Brain Res., 109: 628.PubMedCrossRefGoogle Scholar
  15. Kakihana, R., D.R. Brown, G.E. McClearn, and I.R. Tabershow, 1966, Brain sensitivity to alcohol in inbred mouse strains, Science, 154: 1574.PubMedCrossRefGoogle Scholar
  16. Kalant, H., and W. Grose, 1969, Effects of ethanol and pentobarbital on release of acetylcholine from cerebral cortex slices, J. Pharmacol. Exp. Ther., 158: 386.Google Scholar
  17. Leysen, J.E.,W. Gommeren, and P.M. Laduron, 1978, Spiperone: A ligand of choice for neuroleptic receptors. I. Kinetics and characteristics on in vitro binding, Biochem. Pharmacol., 27:307Google Scholar
  18. Liljequist, S., 1978, Changes in the sensitivity of dopamine receptors in the nucleus accumbens and in the striatum induced by chronic ethanol administration, Acta Pharmacol. et Toxicol., 43: 19.CrossRefGoogle Scholar
  19. McClearn, G.E., and R. Kakihana, 1973, Selective breeding for ethanol sensitivity in mice, Behay. Genet., 3: 409.Google Scholar
  20. Minneman, K.P., M.D. Dibner, B.B. Wolfe, and P.B. Molinoff, 1979a, ßl and ß2-adrenergic receptors are independently regulated, Science, 204: 866.PubMedCrossRefGoogle Scholar
  21. Minneman, K.P., L.R. Hegstrand, and P.B. Molinoff, 1979b, The pharmacological specificity of ßl and ß2-adrenergic receptors in heart and lung in vitro, Mol. Pharmacol., 16: 21.Google Scholar
  22. Tabakoff, B., M. Munoz-Marcus, and J.Z. Fields, submitted, Chronic ethanol feeding produces an increase in muscarinic cholinergic receptors in mouse brain.Google Scholar
  23. Wolfe, B.B., T.K. Harden, J.R. Sporn, and P.B. Molinoff, 1978, Presynaptic modulation of ß-adrenergic receptors in rat cerebral cortex following treatment with antidepressants, J. Pharmacol. Exp. Ther., 207: 446.Google Scholar
  24. Yamamura, H.I., and S.H. Snyder, 1974, Muscarinic cholinergic receptor binding in the longitudinal muscle of the guinea pig ileum, Mol. Pharmacol., 10: 861.Google Scholar
  25. Zahniser, N.R., and P.B. Molinoff, 1978, Effect of guanine nucleotides on striatal dopamine receptors, Nature, 275: 453.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Richard A. Rabin
    • 1
  • Perry B. Molinoff
    • 1
  1. 1.Department of PharmacologyUniversity of Colorado Health Sciences CenterDenverUSA

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