Effects of subchronic nicotine administration on central dopaminergic mechanisms in the rat
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Nicotine was administered acutely and subchronically (14 days) to determine whether various synaptic mechanisms are selectively altered in the nigrostriatal and mesolimbic dopaminergic systems in the rat. When added to tissue preparations in vitro, nicotine had no effects on tyrosine hydroxylase, synaptosomal uptake of [3H]dopamine or binding of [3H]spiperone to D2 receptors in either system. However, acute treatment in vivo stimulated tyrosine hydroxylase activity in the nucleus accumbens. This effect was prevented by pretreatment with a nicotinic antagonist, suggesting that it was mediated by nicotinic receptors. Since subchronic exposure to nicotine had no effect on tyrosine hydroxylase, it appears that tolerance develops to this action. In vivo treatment with nicotine did not alter dopamine uptake or receptor binding. The results suggest that, in doses which result in moderate plasma levels, nicotine has selective stimulant actions on nerve terminals of the mesolimbic system.
Key WordsNicotine dopamine tyrosine hydroxylase brain receptors
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- 1.Andersson, K., Fuxe, K., Eneroth, P., Gustafsson, J.-A., and Agnati, L. F. 1980. Mecamylamine induced blockade of nicotine induced inhibition of gonadotrophin and TSH secretion and of nicotine induced increase of catecholamine turnover in the rat hypothalamus. Acta Physiol. Scand. Suppl. 497:27–29.Google Scholar
- 4.Arqueros, L., Naquira, D., and Zunino, E. 1978. Nicotine-induced release of catecholamines from rat hippocampus and striatum. Biochem. Pharmacol. 27:2667–2674.Google Scholar
- 7.Carr, L. A., Walters, D. E., and Meyer, D. C. 1985. Postnatal development in the rat following pre- or postnatal exposure to nicotine. Res. Commun. Subst. Abuse 6:151–164.Google Scholar
- 12.Imperato, A., Mulas, A., and Di Chiara, G. 1986. Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats. European J. Pharmacol. 132:337–338.Google Scholar
- 14.Konig, J. F. R., and Klippel, R. A. 1963. The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem, Robert E. Krieger, Huntington, N.Y.Google Scholar
- 15.Lichtensteiger, W., Felix, D., Hefti, F., and Schlumpf, M. 1979. Effects of nicotine on dopamine neurons of adult and prenatal mammals and of invertebrates. Pages 15–30,in Remond A., and Izard, C. (eds.), Electrophysiological Effects of Nicotine, Elsevier/North Holland Biomedical Press, Amsterdam.Google Scholar
- 20.Pert, A., and Clarke, P. B. S. 1987. Nicotinic modulation of dopaminergic neurotransmission. Pages 169–189,in Martin, W. R., Van Loon, G. R., Iwamoto, E. T., and Davis, L. (eds.), Tobacco Smoking and nicotine, A Neurobiological Approach, Plenum Press, New York.Google Scholar
- 21.Rosecrans, J. A. 1987. Noncholinergic mechanisms involved in the behavioral and stimulus effects of nicotine, and relationships to the process of nicotine dependenc. Pages 125–139,in Martin, W. R., Van Loon, G. R., Iwamoto, E. T., and Davis, L. (eds.), Tobacco Smoking and Nicotine, A Neurobiological Apporach, Plenum Press, New York.Google Scholar