Cyclodiene insecticides-induced changes in the central depressive effect of chlorpromazine in rats

Abstract

Spontaneous motor activity (SMA), conditioned avoidance response (CAR), muscle coordination (MC) and pentobarbital sleep were tested in rats treated orally for 90 days with tolerated doses of the cyclodiene insecticides, aldrin (1 mg/kg) and endosulfan (2 mg/kg). The same tests were repeated in similarly treated animals after injecting chlorpromazine (4 mg/kg, i.p.). Both the insecticides shortened pentobarbital sleeping time indicating their microsomal enzyme inducing property. Aldrin suppressed SMA, CAR and MC, whereas endosulfan stimulated SMA, inhibited CAR and unaltered MC. However, their concurrent action with CPZ did not result in change in the central depressive effects of the latter, but its potency during the course of its action was altered. Its potency 15 min after injection was greater and 60-180 min later was lesser in these animals than that observed in control animals. This finding was interpreted to suggest that aldrin and endosulfan has quickened the biotransformation of CPZ and thereby shortened its duration of action. A temporary promotion of its potency was accounted to its active metabolites, since prior to inactivation, CPZ is known to be metabolized by the microsomal enzymes to active compounds.