Altered pilocarpine- or chlorpromazine-induced catalepsy after long-term treatment with cholinergic drugs.

Long-term administration of the cholinergic drug pilocarpine attenuates the catalepsy induced by an acute injection of pilocarpine or the deopamine antagonist chlorpromazine. Similar results (i.e., tolerance to pilocarpine and cross-tolerance to chlorpromazine) were noted in mice chronically treated with the cholinesterase inhibitor physostigmine but not in mice chronically treated with neostigmine, a cholinesterase inhibitor which does not penetrate the central nervous system. Mice maintained on the anticholinergic scopolamine showed the opposite effect; there was an increase in the sensitivity to the catalepsy induced by pilocarpine or chlorpromazine. The results suggest that long-term changes in cholinergic receptors may indirectly alter the behavioral effects of drugs which act via dopamine.