DIFFERENTIAL-EFFECTS OF PRETREATMENT WITH NICOTINE AND LOBELINE ON NICOTINE-INDUCED CHANGES IN BODY-TEMPERATURE AND LOCOMOTOR-ACTIVITY IN MICE

Although lobeline and nicotine are both potent ligands at neuronal nic otinic cholinergic receptors, chronic lobeline does not produce the up regulation of nicotinic receptors found with chronic nicotine or the l ess potent agonist anabasine. Since agonist-induced receptor upregulat ion is believed to result from receptor desensitization during chronic treatment, this suggests that lobeline may not desensitize neuronal n icotinic receptors. We addressed this question by comparing lobeline- and nicotine-induced desensitization of the actions of nicotine, using body temperature and locomotor activity as dependent variables. Nicot ine pretreatment reduced the hypothermia and locomotor suppression pro duced by a subsequent nicotine challenge, whereas lobeline pretreatmen t did not. When tested alone, both nicotine and lobeline reduced locom otor activity and body temperature to a similar degree, but lobeline w as significantly less potent. The reductions in activity and temperatu re produced by nicotine were significantly attenuated in chlorisondami ne-treated mice, whereas treatment with this long-lasting nicotinic ch olinergic antagonist did not alter the effects of lobeline. Thus, nico tine and lobeline appear to differ in their ability to produce desensi tization. Furthermore, the effects of these two compounds on locomotor activity and body temperature may be mediated via different mechanism s. (C) 1994 Wiley-Liss, inc.