Nicotine induces disinhibitory behavior in the rat after subchronic peripheral nicotinic acetylcholine receptor blockade

The present study investigated the effects of subchronic nicotine, mecamyla mine and hexamethonium, alone or in combinations, on locomotor activity and behavioral inhibition. Rats were divided into groups and tested for locomo tor activity after acute nicotine. The different groups received vehicle, n icotine, mecamylamine, mecamylamine + nicotine, hexamethonium (two differen t concentrations) and hexamethonium + nicotine injections once a day for 15 days after which they were tested for nicotine-induced locomotor activity again. Acutely, nicotine stimulated locomotor activity, and repeated daily nicotine or hexamethonium + nicotine administration sensitized the animals to this nicotine-induced locomotor stimulation (locomotor sensitization). M ecamylamine administered subchronically in combination with nicotine was ab le to block the induction to locomotor sensitization to nicotine. None of t he nicotinic receptor antagonists induced locomotor sensitization to nicoti ne by themselves. In the elevated plus-maze, subchronic nicotine treatment demonstrated a nicotine-induced behavioral disinhibition, measured as an in crease of time spent in and entries made into open arms. In contrast to the findings regarding locomotor sensitization, none of the antagonists counte racted the induction of this nicotine-induced behavioral disinhibition afte r subchronic co-treatment with nicotine. In addition, both antagonists by t hemselves produced a similar effect as subchronic nicotine, i.e. promoted t he development of nicotine-induced disinhibitory behavior. It was concluded that the induction of locomotor sensitization to nicotine involves stimula tion of central nicotinic acetylcholine receptors, whereas the development of nicotine-induced behavioral disinhibition involves blockade of periphera l nicotinic acetylcholine receptors, and that the latter, but not the forme r, phenomenon from a pharmacological point of view appears to be related to the increased ethanol consummatory behavior observed after subchronic nico tine administration. (C) 2000 Elsevier Science B.V. All rights reserved.