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The Biochemical and Functional Nature of the Nicotine Receptor in Rat Brain

  • L. G. Abood
  • A. Maiti
  • S. Grassi
  • K. S. Salles
Part of the Advances in Behavioral Biology book series (ABBI, volume 31)

Abstract

An investigation has been undertaken of the biochemical nature and neuroanatomical localization of the sites involved in nicotine’s action on the brain. The present report describes studies aimed at 1) the characterization and purification of the nicotine receptor in rat brain; 2) elucidating the psychopharmacologic nature of the receptor using various nicotine analogues and other psychotropic agents; and 3) determining the particular brain regions directly involved in the behavioral effects (e.g., prostration and seizures) of nicotine. The nicotine receptor, which has been purified by affinity chromatography and consists of a major protein with a molecular weight of 58 kdalton and minor components ranging from 47 to 83 kdaltons, does not appear to resemble the nicotinic cholinergic receptor purified from the electric fish. The functional significance of the nicotine receptor has been confirmed by correlating the psychotropic potency of various nicotine analogues with their affinity for the receptor. Evidence is presented for the existence of multiple forms of both the nicotine and nicotinic cholinergic receptors by comparing the binding and psychotropic characteristics of some carbamate esters, nicotine analogues, and various unrelated drugs acting as antagonists to nicotine. In order to determine its neuroanatomical site of psychotropic action, nicotine was injected into cannulae chronically implanted into various brain regions of conscious, freely moving rats. It appears that the primary locus is the vestibular system, particularly that component linked to the cerebellar nodule. Lesioning the cerebellar nodule or inhibiting it with a local anesthetic abolishes the nicotine-induced prostration and increases the number of nicotine and muscarinic cholinergic receptors in hypothalamus and caudate nucleus. It is proposed that the vestibular system, which plays a major role in the processing of sensory-motor information may be involved in the reinforcing and other affective effects of nicotine in man.

Keywords

Nicotine Receptor Fourth Ventricle Vestibular Nucleus Kainic Acid Vestibular System 
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. 1.
    Abood, LG, Reynolds, DT, Booth, H and Bidlack, JM: Sites and mechanisms of nicotine’s action in the brain. Neurosci. Behav. Rev. 5: 479–486, 1981.CrossRefGoogle Scholar
  2. 2.
    Sloan, JW, Martin, WR and Todd, GD: Multiple nicotine binding sites in rat brain P2 fraction. Psychopharmacol. Bull. 19: 402–408, 1983.PubMedGoogle Scholar
  3. 3.
    McLennan, H and York, DH: Cholinergic mechanisms in the caudate nucleus. J. Physiol. Lond. 187: 163–175, 1966.PubMedGoogle Scholar
  4. 4.
    Dreifus, JJ, Kelley, JS and Krnjevic, R: Membrane actions of ACh and nicotine in the cerebral cortex. Fourth Int. Congress on Pharmacol. Abst. Basel: S. Karger, 1969, p 220.Google Scholar
  5. 5.
    Sloan, JW, Todd, GD and Martin, WR: Nature of nicotine binding in rat brain P2 fraction. Pharmacol. Biochem. Behav. 20: 899–909, 1984.PubMedCrossRefGoogle Scholar
  6. 6.
    Marks, MJ and Collins, AC: Characterization of nicotine binding in mouse brain and comparison with the binding of α-bungarotoxin and quinuclidinyl benzilate. Mol. Pharmacol. 22: 554–564, 1982.PubMedGoogle Scholar
  7. 7.
    Sershen, H, Reith, MEA, Lajtha, A and Gennaro, J: Noncholinergic, saturable binding of [3H]nicotine to mouse brain. J. Receptor Res. 2: 1–15, 1981.Google Scholar
  8. 8.
    Clarke, PBS, Schwartz, Rd, Paul, SM, Pert, CB and Pert, A: Nicotinic binding in rat brain. Audioradiographic comparison of [3H]-acetylcholine, [3H]nicotine and [l25I]α-bungarotoxin. J. Neurosci. 5: 1307–1315, 1985.PubMedGoogle Scholar
  9. 9.
    Herndon, RM, Coyle, JT and Addicks, E: Ultrastructural analysis of kainic acid lesion to cerebellar cortex. Neuroscience 5: 1015–1026, 1980.PubMedCrossRefGoogle Scholar
  10. 10.
    Foster, GA and Roberts, PJ.: Morphological and biochemical changes in the cerebellum induced by kainic acid in vivo. J. Neurochem. 34: 1191–1200, 1980.PubMedCrossRefGoogle Scholar
  11. 11.
    Imperato, A, Nicolett, F, Diana, M, Scapagnini, U and DiChiara, G: Fastigial influences on postural tonus as studied by kainate lesions and by local infusion of GABAergic drugs in the rat. Brain Res. 295: 51–63, 1984.PubMedCrossRefGoogle Scholar
  12. 12.
    Maiti, AK: Vestibulo-cerebellum modulates nigrostriatal dopamine synthesis: clinical implications in Parkinsonism. Neuroendocrin. Lett. 4: 196, 1982.Google Scholar
  13. 13.
    Abood, LG, Grassi, S, Costanzo, M and Junig, J: Behavioral and biochemical studies in rats after chronic exposure to nicotine. In (ed.) Sharp, CW, Mechanisms of Tolerance and Dependence, NIDA Monograph 54, pp 348–355, 1984.Google Scholar
  14. 14.
    Marks, MJ, Burch, JB and Collins AC: Effects of chronic nicotine infusion on tolerance development and cholinergic receptors. J. Pharmacol. Exp. Ther. 226: 806–816, 1983.Google Scholar
  15. 15.
    Abood, LG, Latham, W and Grassi, S: Isolation of a nicotine binding site from rat brain by affinity chromatography. Proc. Natl. Acad Sci. USA 80: 3536–3539, 1983.PubMedCrossRefGoogle Scholar
  16. 16.
    Itokawa, H, Toshikazu, I, Haruta, R and Kameyama S: Radical methylation and radical hydroxymethylation of nicotine and quinine. Chem. Bull. 197: 295–297, 1978.Google Scholar
  17. 17.
    Wennogle, LP, Oswald, R, Saitoh, T and Changeux, JP: Dissection of the 66,00-dalton subunit of the acetylcholine receptor. Biochemistry 20: 2492–2497, 1981.PubMedCrossRefGoogle Scholar
  18. 18.
    Morrison, DC: Neurobehavioral and Perceptual Dysfunction in Learning Disabled Children. C.J. Hogrefe, Lewiston, NY, 1985.Google Scholar
  19. 19.
    Bhatara, V, Clark, D, Arnold, L, Gunsett, R and Smeltzer, D: Hyperkinesis treated by vestibular stimulation: An exploratory study. Biol. Psychiat. 3: 269–279, 1981.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • L. G. Abood
    • 1
  • A. Maiti
    • 1
  • S. Grassi
    • 1
  • K. S. Salles
    • 1
  1. 1.Center for Brain ResearchUniversity of Rochester School of Medicine and DentistryRochesterUSA

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