Cholinergic involvement in the action of formetanate on operant behavior in rats.

Formetanate (FMT) is a formamidine acaricide/insecticide with a carbamate moiety in its molecular structure. FMT-induced lethality is reportedly due to inhibition of acetylcholinesterase. Here we report evidence of the neurochemical basis for the sublethal, behavioral effects of FMT in rats. In this experiment, 0.5 mg/kg of FMT (5 min before the 55-min test session) produced a pronounced suppression of response rates in rats trained to lever-press under a multiple fixed-interval 1-min fixed-interval 5-min schedule of milk reinforcement. Injections of scopolamine (0.1 mg/kg) and methylscopolamine (0.1 mg/kg) 15 min before FMT blocked the response rate suppression, whereas pretreatment with either mecamylamine (2 mg/kg) or hexamethonium (2 mg/kg) did not. These data suggest that FMT acts as an indirect agonist on central and peripheral muscarinic receptors, by inhibiting acetylcholinesterase, to produce changes in schedule-controlled responding.