Mutually potentiating effects of mecamylamine and haloperidol in producingcatalepsy in rats

Haloperidol and other dopaminergic (DA) blockers have long been known to in duce catalepsy. Recently, it has been reported that nicotine potentiates th e cataleptic effect of haloperidol. However, this presents a quandary in te rms of neural interactions between nicotinic and DA systems. Nicotine promo tes the release of DA in the striatum, which should attenuate haloperidol-i nduced catalepsy. To resolve this quandary, we assessed haloperidol interac tions with nicotine and its antagonist mecamylamine in five studies. With l ow to moderate doses, we did not find that nicotine potentiated haloperidol -induced catalepsy. However, in two different studies we found that mecamyl amine, a nicotinic antagonist, significantly potentiated the haloperidol-in duced catalepsy. This effect was seen with a dose of mecamylamine which, by itself, did not have any cataleptic effect. These results demonstrate that nicotinic receptor blockade effectively potentiates catalepsy caused by DA blockade. This suggests that previously seen nicotine-induced potentiation of catalepsy may have been due to its desensitizing effect. Perhaps the us e of nicotinic antagonists such as mecamylamine or nicotine + mecamylamine combinations would provide a useful adjunct to DA antagonist therapy in mot or disorders such as Tourette's syndrome. Drug Dev. Res. 47:90-96, 1999. (C ) 1999 Wiley-Liss, Inc.