Acute effects of nicotine on prolactin release in the rat: agonist and antagonist effects of a single injection of nicotine

BA Hulihan-Giblin, MD Lumpkin and KJ Kellar

Department of Pharmacology, Georgetown University School of Medicine, Washington, District of Columbia.

The effects of nicotine on prolactin release were studied in conscious, unrestrained rats in which an indwelling jugular cannula allowed multiple samplings of blood after i.v. administration of nicotine. Intravenous administration of nicotine bitartrate dihydrate increases plasma prolactin concentrations in a dose-dependent manner with an ED50 of approximately 100 micrograms/kg (200 nmol/kg) and this effect is blocked completely by pretreatment with mecamylamine, indicating that it is mediated by a nicotinic cholinergic receptor. Intracerebral ventricular injection of 1 microgram of nicotine also increases plasma prolactin levels, but i.v. injection of this same amount of nicotine has no effect, indicating that nicotine acts within the brain to release prolactin. A single i.v. injection of nicotine resulted in desensitization of the prolactin response to a subsequent injection of nicotine given 1 to 2 hr later, thus confirming a previous report by Sharp and Beyer (J. Pharmacol. Exp. Ther. 238: 486-491, 1986). The prolactin response to nicotine was restored within 24 hr after a single injection. The acute desensitization after a single injection of nicotine appears to be specific to release of prolactin by nicotine because the prolactin response to morphine was unaffected 1 hr after injection of nicotine. A single injection of nicotine appears to desensitize the prolactin response to a subsequent injection of nicotine with an ED50 of approximately 20 micrograms/kg (40 nmol/kg), indicating that nicotine is even more potent in stimulating desensitization of nicotinic cholinergic receptors than in stimulating prolactin release. These results support the concept that nicotine acts as a time-averaged antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 252, Issue 1, pp. 15-20, 01/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				Y. Xiao, H. Fan, J. L. Musachio, Z.-L. Wei, S. K. Chellappan, A. P. Kozikowski, and K. J. Kellar Sazetidine-A, A Novel Ligand That Desensitizes {alpha}4beta2 Nicotinic Acetylcholine Receptors without Activating Them Mol. Pharmacol., October 1, 2006; 70(4): 1454 - 1460. [Abstract] [Full Text] [PDF]

				J. H. Mendelson, M. B. Sholar, N. H. Mutschler, M. Jaszyna-Gasior, N. V. Goletiani, A. J. Siegel, and N. K. Mello Effects of Intravenous Cocaine and Cigarette Smoking on Luteinizing Hormone, Testosterone, and Prolactin in Men J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 339 - 348. [Abstract] [Full Text] [PDF]

				Y. Xiao, R. D. Smith, F. S. Caruso, and K. J. Kellar Blockade of Rat alpha 3beta 4 Nicotinic Receptor Function by Methadone, Its Metabolites, and Structural Analogs J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 366 - 371. [Abstract] [Full Text] [PDF]

				E. L. Meyer, Y. Xiao, and K. J. Kellar Agonist Regulation of Rat alpha 3beta 4 Nicotinic Acetylcholine Receptors Stably Expressed in Human Embryonic Kidney 293 Cells Mol. Pharmacol., September 1, 2001; 60(3): 568 - 576. [Abstract] [Full Text] [PDF]

				D. C. Perry, M. I. Dávila-García, C. A. Stockmeier, and K. J. Kellar Increased Nicotinic Receptors in Brains from Smokers: Membrane Binding and Autoradiography Studies J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1545 - 1552. [Abstract] [Full Text]

				F. Olale, V. Gerzanich, A. Kuryatov, F. Wang, and J. Lindstrom Chronic Nicotine Exposure Differentially Affects the Function of Human alpha 3, alpha 4, and alpha 7 Neuronal Nicotinic Receptor Subtypes J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 675 - 683. [Abstract] [Full Text]

				K. Fattinger, D. Verotta, and N. L. Benowitz J. Pharmacol. Exp. Ther., June 1, 1997; 281(3): 1238 - 1246. [Abstract] [Full Text]