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  • Title: Differential alteration in striatal dopaminergic and cortical serotonergic receptors induced by repeated administration of haloperidol or centbutindole in rats.
    Author: Gulati A, Srimal RC, Dhawan BN.
    Journal: Pharmacology; 1988; 36(6):396-404. PubMed ID: 2901759.
    Abstract:
    Centbutindole is a new neuroleptic drug having a pharmacological profile similar to haloperidol, but it does not cause hypothermia and has a higher separation between doses causing catalepsy and neurolepsy. The interactions of centbutindole with striatal dopamine and cortical 5-HT2 receptors have been studied along with haloperidol following 3 weeks of administration. Rats received haloperidol (1.0 mg/kg, p.o.), centbutindole (0.5 mg/kg, p.o.) or saline daily for 21 days. Following drug withdrawal for 3 days, apomorphine (0.1-1.0 mg/kg, i.p.) or 5-hydroxytryptamine (5-HTP, 50-200 mg/kg, i.p.) was injected. Apomorphine-induced stereotyped behaviour was potentiated in the haloperidol-treated rats, while the 5-HTP-induced behavioural syndrome was increased in centbutindole-treated rats. Receptor binding studies indicated an increase in the maximal binding capacity Bmax of striatal dopamine receptor (29.4%) in haloperidol-treated and of cortical 5-HT2 receptor (17.8%) in centbutindole-treated animals. No change in the apparent dissociation constant Kd was observed. It is concluded that repeated treatment with haloperidol produced striatal dopamine receptor supersensitivity while centbutindole treatment produced cortical serotonergic receptor supersensitivity.
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