Blockade of Nicotine Self-Administration with Nicotinic Antagonists in Rats

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• 作者：Watkins ; Shelly S. ; Epping-Jordan ; Mark P. ; et. al.
• 关键词：Nicotine ; Self-administration ; Reinforcement ; Mecamylamine ; Dihydro-β ; -erythroidine ; Rat
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：1999
• 出版时间：April, 1999
• 年：1999
• 卷：62
• 期：4
• 页码：743-751
• 全文大小：119 K

文摘

The reinforcing properties of a variety of drugs abused by humans have been investigated using the technique of intravenous self-administration in the rat. To examine the effect of nicotine dose on nicotine self-administration, Wistar rats were allowed to self-administer various doses of nicotine using a within-subjects Latin square design. An inverted U-shaped dose–response curve was obtained, with the highest rates of responding at the 0.03 mg/kg/inf dose. With 1-h daily nicotine self-administration sessions, rats did not appear dependent on nicotine 24 h later, as indicated by the absence of somatic signs of withdrawal after subcutaneous injection of a nicotinic acetylcholine receptor antagonist, mecamylamine (0.57 mg/kg). In another set of studies, pretreatment with subcutaneous mecamylamine or dihydro-β-erythroidine, two nicotinic acetylcholine receptor antagonists, resulted in significant dose-dependent reductions in nicotine self-administration, at two nicotine doses (0.03 and 0.06 mg/kg/inf). These results indicate that nicotine is an effective reinforcer in Wistar rats under the present parameters, and that these reinforcing effects are mediated by activation of nicotinic acetylcholine receptors. Publisher: Elsevier Science Language of Publication: English Item Identifier: S0091-3057(98)00226-3 Publication Type: Article ISSN: 0091-3057 Cited by:

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2. Grottick, A.J.; Wyler, R.; Higgins, G.A.,""A study of the nicotinic agonist SIB-1553A on locomotion, and attention as measured by the five-choice serial reaction time task""Pharmacology Biochemistry and Behavior2001pp. 505-513
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4. Kenny, Paul J.; Markou, Athina,""Neurobiology of the nicotine withdrawal syndrome""Pharmacology Biochemistry and Behavior2001pp. 531-549
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5. Young, John M.; Douglas Shytle, R.; Sanberg, Paul R.; George, Tony P.,""Mecamylamine: new therapeutic uses and toxicity/risk profile""Clinical Therapeutics2001pp. 532-565
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6. Rose, Jed E.; Behm, Frederique M.; Westman, Eric C.,""Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking""Pharmacology Biochemistry and Behavior2001pp. 187-197
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7. Glick, Stanley D.; Maisonneuve, Isabelle M.; Kitchen, Barbara A.,""Modulation of nicotine self-administration in rats by combination therapy with agents blocking a3b4 nicotinic receptors""European Journal of Pharmacology2002pp. 185-191
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9. Brower, Victoria G.; Fu, Yitong; Matta, Shannon G.; Sharp, Burt M.,""Rat strain differences in nicotine self-administration using an unlimited access paradigm""Brain Research2002pp. 12-20
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10. Steinmiller, Caren L.; Maisonneuve, Isabelle M.; Glick, Stanley D.,""Effects of dextromethorphan on dopamine release in the nucleus accumbens: Interactions with morphine""Pharmacology Biochemistry and Behavior2003pp. 803-810
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11. Walker, Diana J.; Zacny, James P.,""Bitonic dose-response functions for reinforcing and self-reported effects of nitrous oxide in humans""Pharmacology Biochemistry and Behavior2003pp. 851-857
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12. Semenova, Svetlana; Bespalov, Anton; Markou, Athina,""Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration""European Journal of Pharmacology2003pp. 99-110
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Footnotes:

1. Current address: Glaxo Wellcome Experimental Research S.A., Institut de Biologie Cellulaire et de Morphologie (IBCM), Universite de Lausanne, Rue du Bugnon 9, CH-1005, Lausanne, Switzerland