M. Ericson et al., Nicotine induces disinhibitory behavior in the rat after subchronic peripheral nicotinic acetylcholine receptor blockade, EUR J PHARM, 397(1), 2000, pp. 103-111
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.