Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1989 Sep;98(1):71–78. doi: 10.1111/j.1476-5381.1989.tb16864.x

Effect of acute and subchronic nicotine treatment on cortical acetylcholine release and on nicotinic receptors in rats and guinea-pigs.

A Nordberg 1, L Romanelli 1, A Sundwall 1, C Bianchi 1, L Beani 1
PMCID: PMC1854650  PMID: 2804554

Abstract

1. The effect of acute and chronic (16 days) administration of nicotine on cortical acetylcholine (ACh) release, gross behaviour and brain nicotinic binding sites was investigated in rats and guinea-pigs. 2. The drug, injected either subcutaneously (0.45-0.90 mg kg-1) or intracerebroventricularly (1, 3 and 5 micrograms) increased the cortical ACh release, in a dose-dependent manner, through mecamylamine-sensitive receptors for 1-2 h in both species. 3. Chronic treatment significantly increased basal ACh release in the rat and slightly lowered it in the guinea-pig, but the response to a challenging dose of nicotine was proportionally maintained in both species. 4. The number of nicotinic receptors was four times higher in the rat than in the guinea-pig and was not dependent on the radioligand used ([3H]-nicotine or [3H]-ACh, in the presence of atropine) to determine this. The nicotinic binding sites showed an apparent increase in chronically treated rats but no change in guinea-pigs. 5. Tolerance to the inhibitory effect of the drug, assessed with the T maze test, was found in the rat. No apparent change in gross behaviour was detected in the guinea-pig. 6. It is concluded that chronic nicotine treatment causes evident tolerance to its inhibitory effect on behaviour in the rat, but no adaptation to its excitatory properties on the cholinergic brain structures in rats and guinea-pigs.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aceto M. D., Martin B. R. Central actions of nicotine. Med Res Rev. 1982 Jan-Mar;2(1):43–62. doi: 10.1002/med.2610020104. [DOI] [PubMed] [Google Scholar]
  2. Adem A., Synnergren B., Botros M., Ohman B., Winblad B., Nordberg A. [3H]acetylcholine nicotinic recognition sites in human brain: characterization of agonist binding. Neurosci Lett. 1987 Dec 29;83(3):298–302. doi: 10.1016/0304-3940(87)90103-0. [DOI] [PubMed] [Google Scholar]
  3. Armitage A. K., Hall G. H., Sellers C. M. Effects of nicotine on electrocortical activity and acetylcholine release from the cat cerebral cortex. Br J Pharmacol. 1969 Jan;35(1):152–160. doi: 10.1111/j.1476-5381.1969.tb07976.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Balfour D. J. The effects of nicotine on brain neurotransmitter systems. Pharmacol Ther. 1982;16(2):269–282. doi: 10.1016/0163-7258(82)90058-4. [DOI] [PubMed] [Google Scholar]
  5. Beani L., Bianchi C., Nilsson L., Nordberg A., Romanelli L., Sivilotti L. The effect of nicotine and cytisine on 3H-acetylcholine release from cortical slices of guinea-pig brain. Naunyn Schmiedebergs Arch Pharmacol. 1985 Nov;331(2-3):293–296. doi: 10.1007/BF00634252. [DOI] [PubMed] [Google Scholar]
  6. Beani L., Bianchi C., Santinoceto L., Marchetti P. The cerebral acetylcholine release in conscious rabbits with semi-permanently implanted epidural cups. Int J Neuropharmacol. 1968 Sep;7(5):469–481. doi: 10.1016/0028-3908(68)90046-4. [DOI] [PubMed] [Google Scholar]
  7. Benwell M. E., Balfour D. J., Anderson J. M. Evidence that tobacco smoking increases the density of (-)-[3H]nicotine binding sites in human brain. J Neurochem. 1988 Apr;50(4):1243–1247. doi: 10.1111/j.1471-4159.1988.tb10600.x. [DOI] [PubMed] [Google Scholar]
  8. Casamenti F., Bianchi C., Beani L., Pepeu G. Effect of haloperidol and pimozide on acetylcholine output from the cerebral cortex in rats and guinea pigs. Eur J Pharmacol. 1980 Jul 25;65(2-3):279–284. doi: 10.1016/0014-2999(80)90401-x. [DOI] [PubMed] [Google Scholar]
  9. Changeux J. P., Devillers-Thiéry A., Chemouilli P. Acetylcholine receptor: an allosteric protein. Science. 1984 Sep 21;225(4668):1335–1345. doi: 10.1126/science.6382611. [DOI] [PubMed] [Google Scholar]
  10. Clarke P. B., Hommer D. W., Pert A., Skirboll L. R. Electrophysiological actions of nicotine on substantia nigra single units. Br J Pharmacol. 1985 Aug;85(4):827–835. doi: 10.1111/j.1476-5381.1985.tb11081.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Clarke P. B., Pert A. Autoradiographic evidence for nicotine receptors on nigrostriatal and mesolimbic dopaminergic neurons. Brain Res. 1985 Dec 2;348(2):355–358. doi: 10.1016/0006-8993(85)90456-1. [DOI] [PubMed] [Google Scholar]
  12. Curvall M., Kazemi-Vala E., Enzell C. R. Simultaneous determination of nicotine and cotinine in plasma using capillary column gas chromatography with nitrogen-sensitive detection. J Chromatogr. 1982 Nov 12;232(2):283–293. doi: 10.1016/s0378-4347(00)84168-7. [DOI] [PubMed] [Google Scholar]
  13. Egan T. M., North R. A. Actions of acetylcholine and nicotine on rat locus coeruleus neurons in vitro. Neuroscience. 1986 Oct;19(2):565–571. doi: 10.1016/0306-4522(86)90281-2. [DOI] [PubMed] [Google Scholar]
  14. Engberg G., Svensson T. H. Pharmacological analysis of a cholinergic receptor mediated regulation of brain norepinephrine neurons. J Neural Transm. 1980;49(3):137–150. doi: 10.1007/BF01245220. [DOI] [PubMed] [Google Scholar]
  15. Erickson C. K., Graham D. T., U'prichard T. Cortical cups for collecting free acetylcholine in awake rats. Pharmacol Biochem Behav. 1973 Nov-Dec;1(6):743–746. doi: 10.1016/0091-3057(73)90041-5. [DOI] [PubMed] [Google Scholar]
  16. Giorguieff-Chesselet M. F., Kemel M. L., Wandscheer D., Glowinski J. Regulation of dopamine release by presynaptic nicotinic receptors in rat striatal slices: effect of nicotine in a low concentration. Life Sci. 1979 Oct 1;25(14):1257–1262. doi: 10.1016/0024-3205(79)90469-7. [DOI] [PubMed] [Google Scholar]
  17. Goldberg S. R., Spealman R. D., Goldberg D. M. Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science. 1981 Oct 30;214(4520):573–575. doi: 10.1126/science.7291998. [DOI] [PubMed] [Google Scholar]
  18. Goodman F. R. Effects of nicotine on distribution and release of 14C-norepinephrine and 14C-dopamine in rat brain striatum and hypothalamus slices. Neuropharmacology. 1974 Nov;13(10-11):1025–1032. doi: 10.1016/0028-3908(74)90093-8. [DOI] [PubMed] [Google Scholar]
  19. Hajós M., Engberg G. Role of primary sensory neurons in the central effects of nicotine. Psychopharmacology (Berl) 1988;94(4):468–470. doi: 10.1007/BF00212839. [DOI] [PubMed] [Google Scholar]
  20. Hall G. H. Pharmacological responses to the intracerebral administration of nicotine. Pharmacol Ther. 1981;15(2):223–238. doi: 10.1016/0163-7258(81)90043-7. [DOI] [PubMed] [Google Scholar]
  21. Hall G. H., Turner D. M. Effects of nicotine on the release of 3 H-noradrenaline from the hypothalamus. Biochem Pharmacol. 1972 Jul 1;21(13):1829–1838. doi: 10.1016/0006-2952(72)90179-7. [DOI] [PubMed] [Google Scholar]
  22. Henningfield J. E., Miyasato K., Jasinski D. R. Cigarette smokers self-administer intravenous nicotine. Pharmacol Biochem Behav. 1983 Nov;19(5):887–890. doi: 10.1016/0091-3057(83)90099-0. [DOI] [PubMed] [Google Scholar]
  23. Härfstrand A., Fuxe K., Andersson K., Agnati L., Janson A. M., Nordberg A. Partial di-mesencephalic hemitransections produce disappearance of [3H]nicotine binding in discrete regions of rat brain. Acta Physiol Scand. 1987 May;130(1):161–163. doi: 10.1111/j.1748-1716.1987.tb08122.x. [DOI] [PubMed] [Google Scholar]
  24. Ksir C., Hakan R., Hall D. P., Jr, Kellar K. J. Exposure to nicotine enhances the behavioral stimulant effect of nicotine and increases binding of [3H]acetylcholine to nicotinic receptors. Neuropharmacology. 1985 Jun;24(6):527–531. doi: 10.1016/0028-3908(85)90058-9. [DOI] [PubMed] [Google Scholar]
  25. Larsson C., Nordberg A. Comparative analysis of nicotine-like receptor-ligand interactions in rodent brain homogenate. J Neurochem. 1985 Jul;45(1):24–31. doi: 10.1111/j.1471-4159.1985.tb05469.x. [DOI] [PubMed] [Google Scholar]
  26. Mereu G., Yoon K. W., Boi V., Gessa G. L., Naes L., Westfall T. C. Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine. Eur J Pharmacol. 1987 Sep 23;141(3):395–399. doi: 10.1016/0014-2999(87)90556-5. [DOI] [PubMed] [Google Scholar]
  27. Meyer E. M., Arendash G. W., Judkins J. H., Ying L., Wade C., Kem W. R. Effects of nucleus basalis lesions on the muscarinic and nicotinic modulation of [3H]acetylcholine release in the rat cerebral cortex. J Neurochem. 1987 Dec;49(6):1758–1762. doi: 10.1111/j.1471-4159.1987.tb02433.x. [DOI] [PubMed] [Google Scholar]
  28. Morley B. J., Kemp G. E., Salvaterra P. alpha-Bungarotoxin binding sites in the CNS. Life Sci. 1979 Mar 5;24(10):859–872. doi: 10.1016/0024-3205(79)90335-7. [DOI] [PubMed] [Google Scholar]
  29. Morley B. J. The properties of brain nicotine receptors. Pharmacol Ther. 1981;15(1):111–122. doi: 10.1016/0163-7258(81)90020-6. [DOI] [PubMed] [Google Scholar]
  30. Nordberg A., Winblad B. Reduced number of [3H]nicotine and [3H]acetylcholine binding sites in the frontal cortex of Alzheimer brains. Neurosci Lett. 1986 Dec 3;72(1):115–119. doi: 10.1016/0304-3940(86)90629-4. [DOI] [PubMed] [Google Scholar]
  31. Romanelli L., Ohman B., Adem A., Nordberg A. Subchronic treatment of rats with nicotine: interconversion of nicotinic receptor subtypes in brain. Eur J Pharmacol. 1988 Mar 29;148(2):289–291. doi: 10.1016/0014-2999(88)90577-8. [DOI] [PubMed] [Google Scholar]
  32. Rowell P. P., Carr L. A., Garner A. C. Stimulation of [3H]dopamine release by nicotine in rat nucleus accumbens. J Neurochem. 1987 Nov;49(5):1449–1454. doi: 10.1111/j.1471-4159.1987.tb01013.x. [DOI] [PubMed] [Google Scholar]
  33. Rowell P. P., Winkler D. L. Nicotinic stimulation of [3H]acetylcholine release from mouse cerebral cortical synaptosomes. J Neurochem. 1984 Dec;43(6):1593–1598. doi: 10.1111/j.1471-4159.1984.tb06083.x. [DOI] [PubMed] [Google Scholar]
  34. Schwartz R. D., Lehmann J., Kellar K. J. Presynaptic nicotinic cholinergic receptors labeled by [3H]acetylcholine on catecholamine and serotonin axons in brain. J Neurochem. 1984 May;42(5):1495–1498. doi: 10.1111/j.1471-4159.1984.tb02818.x. [DOI] [PubMed] [Google Scholar]
  35. Stolerman I. P., Fink R., Jarvik M. E. Acute and chronic tolerance to nicotine measured by activity in rats. Psychopharmacologia. 1973 Jun 29;30(4):329–342. doi: 10.1007/BF00429192. [DOI] [PubMed] [Google Scholar]
  36. Westfall T. C., Grant H., Perry H. Release of dopamine and 5-hydroxytryptamine from rat striatal slices following activation of nicotinic cholinergic receptors. Gen Pharmacol. 1983;14(3):321–325. doi: 10.1016/0306-3623(83)90037-x. [DOI] [PubMed] [Google Scholar]
  37. Whitehouse P. J., Martino A. M., Antuono P. G., Lowenstein P. R., Coyle J. T., Price D. L., Kellar K. J. Nicotinic acetylcholine binding sites in Alzheimer's disease. Brain Res. 1986 Apr 16;371(1):146–151. doi: 10.1016/0006-8993(86)90819-x. [DOI] [PubMed] [Google Scholar]
  38. Wonnacott S. Brain nicotine binding sites. Hum Toxicol. 1987 Sep;6(5):343–353. doi: 10.1177/096032718700600502. [DOI] [PubMed] [Google Scholar]
  39. Yoshida K., Kato Y., Imura H. Nicotine-induced release of noradrenaline from hypothalamic synaptosomes. Brain Res. 1980 Jan 27;182(2):361–368. doi: 10.1016/0006-8993(80)91194-4. [DOI] [PubMed] [Google Scholar]
  40. Zhang X., Stjernlöf P., Adem A., Nordberg A. Anatoxin-a a potent ligand for nicotinic cholinergic receptors in rat brain. Eur J Pharmacol. 1987 Mar 31;135(3):457–458. doi: 10.1016/0014-2999(87)90702-3. [DOI] [PubMed] [Google Scholar]
  41. de la Garza R., Bickford-Wimer P. C., Hoffer B. J., Freedman R. Heterogeneity of nicotine actions in the rat cerebellum: an in vivo electrophysiologic study. J Pharmacol Exp Ther. 1987 Feb;240(2):689–695. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES