The mechanisms of action of atypical and novel antipsychotic drugs: Actions of typical and atypical antipsychotics on tuberoinfundibular dopamine neurons

The activity of tuberoinfundibular dopamine neurons, as judged from the accumulation of dihydroxyphenylalanine (DOPA) after the inhibition of decarboxylase activity, was unaltered following the acute administration of the typical antipsychotics haloperidol, cis-flupentixol, chlorpromazine, or fluphenazine. In contrast, a significant increase in the activity of tuberoinfundibular dopamine neurons was elicited by the purported atypical antipsychotics clozapine, melperone, thioridazine, setoperone, and RMI 81582. The clozapine-induced increase in the activity of tuberoinfundibular dopamine neurons was antagonized by the D₁ agonist SKF 38393, but not by the D₂ agonist quinpirole. The stimulatory effects of atypical antipsychotics on the activity of these hypothalamic dopamine neurons was mimicked by neurotensin and its analogue [D-Trp¹¹]-neurotensin. Moreover, like typical antipsychotics, neurotensin and its analogue also increased serum concentrations of corticosterone. The production of an acute activation of tuberoinfundibular dopamine neurons, which is sensitive to D₁ receptor activation and may be mediated by neurotensin, appears to be an effect that distinguishes typical and atypical antipsychotics.