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Studies on the time course and the effect of cholinergic and adrenergic receptor blockers on the stimulus effect of nicotine

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Abstract

This study investigated the stimulus property of nicotine in the rat. The primary objectives of the study were 1. to determine the time course of the nicotine stimulus and its relationship to brain levels of the drug and 2. to determine whether the nicotine stimulus is dependent upon the integrity of specific neurotransmitter systems. A lever choice discrimination was used. After injection of nicotine, depression of one lever in an operant test chamber resulted in food reinforcement according to a variable interval schedule of 15 sec. When saline was administered, the opposite lever was reinforced. A high degree of discriminated responding was observed when either 400 Μg/kg or 200 Μg/kg of nicotine was used as a discriminative stimulus. The degree of discrimination decreased as the length of the time period between the injection of nicotine and the test of discrimination was increased. This decline in discrimination was similar to the decline in brain levels of nicotine suggesting that nicotine discrimination is directly related to the concentration of nicotine in the brain. Atropine, mecamylamine, dibenamine, propranolol and α-methyl-para-tyrosine (AMPT) were all tested, in a range of doses, for effects upon nicotine discrimination. Of these, only mecamylamine antagonized the nicotine stimulus. These results indicate that the stimulus effect of nicotine is mediated specifically through nicotinic-cholinergic receptors and not muscarinic-cholinergic or adrenergic receptors.

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A preliminary report of this investigation appeared in the Pharmacologist 15, 452 (1973).

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Hirschhorn, I.D., Rosecrans, J.A. Studies on the time course and the effect of cholinergic and adrenergic receptor blockers on the stimulus effect of nicotine. Psychopharmacologia 40, 109–120 (1974). https://doi.org/10.1007/BF00421360

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  • DOI: https://doi.org/10.1007/BF00421360

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