Alteration in dopaminergic and muscarinic cholinergic receptors after subchronic treatment with haloperidol in the developing rat brain.
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 (Bmax) without alteration in a dissociation constant (KD). 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 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 to be due to alteration in the striatal [3H]QNB binding.
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010862:Pilocarpine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology
D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D013134:Spiperone; D011813:Quinuclidinyl Benzilate; D006220:Haloperidol