부산대학교 도서관

Our earlier observation that the antipsychotic drug haloperidol in the absence of dopamine increases cAMP formation and prolactin release in two prolactin-producing cell lines expressing rat dopamine D2receptors (GH3, GH4ZR7), but not in similar cells devoid of D2receptors (GH4C1), prompted us to suggest that haloperidol may act as an inverse (or negative) agonist, rather than as a neutral antagonist, at the D2receptor (Nilsson and Eriksson 1993). In the present study it is shown that haloperidol elicits a dose-dependent increase in prolactin release also in prolactin-producing GH4C1cells transfected with the human dopamine D2receptor (short isoform) (GH4C1-hD2s); in addition, it is shown that another antipsychotic drug, flupenthixol, also causes prolactin release per se in this cell line. The effect of haloperidol on prolactin release in GH4C1-hD2s is calcium dependent and counteracted by pretreatment either with the D2receptor agonist R(−)-n-propylnorapomorphine or with a D2receptor antagonist that does not affect prolactin release per se (raclopride). In addition, pretreatment with the alkylating compound phenoxybenzamine at a concentration causing a marked reduction of D2receptor density in GH4C1-hD2s cells significantly counteracted haloperidol-induced prolactin release.Neuropsychopharmacology (1996) 15 53–61.