Chlorisondamine inhibits the nicotine-induced stimulation of c-fos in the pigeon brain for up to 2 weeks.

Chlorisondamine is a charged molecule that acts as long-acting nicotinic antagonist in many species, including pigeon. Evidence indicates that, despite the charged nature of chlorisondamine, it blocks some central effects of nicotine. The present study examined the time course of chlorisondamine's blockade of nicotine-induced c-fos expression in the pigeon brain. Chlorisondamine's central blockade was examined from 1 hr to 28 days prior to nicotine administration. Nicotine stimulated increases in c-fos mRNA in the hippocampus, hyperstriatum accessorium, hyperstriatum ventrale, nucleus accumbens, bulbus olfactorius, paleostriatum augmentatum, and stratum griseum et fibrosum superficiale. Nicotinic receptors labeled by (125)I]-epibatidine were not always found in the same regions as nicotine-induced increases in c-fos expression. Acute chlorisondamine increased the level of c-fos mRNA in the cerebellum, hippocampus, hyperstriatum accessorium, locus parolfactorius, nucleus accumbens, tectum opticum, paleostriatum augmentatum, and stratum griseum et fibrosum superficiale but had no effect on its own 24 hr after administration. Chlorisondamine blocked nicotine-induced increases in c-fos RNA for 4 days in the nucleus accumbens, a week in the bulbus olfactorius, and 2 weeks in the stratum griseum et fibrosum superficiale. The time course of chlorisondamine's blockade of nicotine-induced c-fos expression is consistent with the time course of the ability of chlorisondamine to block behavioral and physiological responses to nicotine.