Alteration in dopaminergic and muscarinic cholinergic receptors after subchronic treatment with haloperidol in the developing rat brain.

Abstract

Influence of subchronic treatment with haloperidol (0.5-5.0 mg/kg for 10 days, twice a day) on sensitivity of both central dopaminergic (DA) and muscarinic cholinergic (ACh [acetylcholine]) receptors was behaviorally and neurochemically investigated 4 days after withdrawal stage of the drug in the developing rat aged 28 days. An i.p. injection of apomorphine (0.2 mg/kg) induced locomotor stimulation more effectively in haloperidol-treated animals than in controls. Scatchard analysis of the specific [3H]spiperone binding to the striatal membranes showed that haloperidol treatment increased the maximal number of binding sites (Bmax) without alteration in a Kd. Pilocarpine (100 and 150 mg/kg) was less effective in inducing catalepsy in the treated animals than in controls, but the treatment did not induce any alteration in saturation parameters of specific [3H]quinuclidinyl benzilate ([3H]QNB) binding to the homogenates of striatum, mesolimbic area and hippocampus. A decrease in Bmax in the striatal [3H]spiperone binding by chronic haloperidol treatment underlies DA receptor hypersensitivity in developing rats. Behavioral muscarinic hyposensitivity caused by chronic haloperidol may not be due to alteration in the striatal [3H]QNB binding.