ALTERATION IN DOPAMINERGIC AND MUSCARINIC CHOLINERGIC RECEPTORS AFTER SUBCHRONIC TREATMENT WITH HALOPERIDOL IN THE DEVELOPING RAT BRAIN

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Influence of subchronic treatment with haloperidol (0.5 to 5.0 mg/kg for 10 days, twice a day) on sensitivity of both central dopaminergic (DA) and muscarinic cholinergic (ACH) 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 produced an increase in the maximal number of binding sites (B_<max>) without alteration in a dissociation constant (K_D). Pilocarpine (100 and 150 mg/kg) was less effective in inducing catalepsy in the treated animals than in controls, although 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. It is suggested that a decrease in B_<max> 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 to be due to alteration in the striatal [^3H] QNB binding.
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