Behavioral Effects of Single and Repeated Treatments with the Combination of D1 and D2 Antagonists
It is generally accepted that cerebral D2 dopamine receptors mediate the antidopaminergic activity of neuroleptics (Creese et al. 1976). This view is supported by the observations that all clinically effective antipsychotics are either mixed D1/D2 blockers or selective D2 dopamine antagonists (Christensen et al. 1984) and that a high correlation exists between the ability of neuroleptics to interact with the D2 receptors “in vitro” and their clinical efficacy (Seeman 1980). Nevertheless, the substituted benzamide sulpiride, which selectively blocks D2 dopamine receptors, is much weaker than classic neuroleptics in suppressing dopamine mediated behaviours (Jenner et al. 1978) and fails to antagonize apomorphine-induced stereotyped behaviour and to induce catalepsy (Costall and Naylor 1975; Jenner et al. 1978; Serra et al. 1983). In contrast, the selective D1 antagonist SCH 23390 does induce catalepsy and inhibits agonist-elicited stereotypy and hyperactivity (Iorio et al. 1983; Christensen et al. 1984), thus behaving as a classic neuroleptic agent. Therefore some antidopaminergic effects could be mediated by the concomitant blockade of D1 receptors which could contribute to the full activity of the typical antipsychotic drugs.
KeywordsStereotyped Behaviour Motility Count Subthreshold Dose Stereotyped Response Typical Antipsychotic Drug
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