DOPAMINERGIC AND CHOLINERGIC INTERACTION IN CATALEPTIC RESPONSES IN MICE

The cataleptogenic effects of haloperidol, a dopamine D2 receptor anta gonist; SCH23390, a D1 receptor antagonist; physostigmine, a cholinest erase inhibitor; and pilocarpine, a muscarinic M1 receptor agonist, we re challenged by pretreatment of mice with SKF38393, a dopamine D1 rec eptor agonist; apomorphine, a dopamine D1/D2 receptor agonist (mainly D2 receptor); pirenzepine, a muscarinic M1 receptor antagonist; and sc opolamine, a muscarinic M1/M2 receptor antagonist. The effect of physo stigmine and pilocarpine on haloperidol and SCH23390 cataleptic respon ses was also examined. Each of the challenging agents blocked one or m ore of the cataleptogenic agents, but only scopolamine blocked all fou r. Pirenzepine blocked cataleptic responses induced by SCH23390 and pi locarpine, but not those by haloperidol and physostigmine. The results of this study suggest that the action of physostigmine (endogenous ac etylcholine) on M2 receptors might be more potent than that on muscari nic M1 receptors. A further interesting observation was that the halop eridol-induced catalepsy was enhanced by physostigmine pretreatment, b ut not by pilocarpine pretreatment, whereas the SCH23390-induced catal epsy showed the opposite spectrum of enhancement by the two cholinergi c agonists. We conclude that, although the four cataleptogenic agents act via the dopaminergic-cholinergic systems, their pharmacological di fferences may be due largely to the different receptor subtypes that a re involved in the mediation of catalepsy produced by each agent. Thus , dopamine receptors not only influence the cholinergic muscarinic rec eptors, but muscarinic M1 and M2 receptors also might mediate dopamine DI and D2 receptor responses, respectively. The results suggest that there are, at the least, relationships between muscarinic M1 receptors and dopaminergic DI receptors, and between muscarinic M2 receptors an d dopaminergic D2 receptors. Dopamine D1 and D2 receptors may interact in a synergistic fashion on dopaminergic systems, but act independent ly,of each other in influencing other system such as cholinergic neuro ns. (C) 1997 Elsevier Science Inc.