Biochemical and behavioral effects of boldine and glaucine on dopamine systems

The aporphine alkaloids boldine and glaucine have been reported to show "ne uroleptic-like" actions in mice, suggesting that they may act as dopamine a ntagonists. We have found that in vitro boldine displaces specific striatal [H-3]-SCH 23390 binding with IC50 = 0.4 mu M and [H-3]-raclopride binding with IC50 = 0.5 mu M, while the affinities of glaucine at the same sites ar e an order of magnitude lower. In vivo, however, 40 mg/kg boldine (IP) did not modify specific striatal [H-3]-raclopride binding and only decreased [H -3]-SCH 23390 binding by 25%. On the other hand, 40 mg/kg glaucine (IP) dis placed both radioligands by about 50%. Behaviors (climbing, sniffing, groom ing) elicited in mice by apomorphine (0.75 mg/kg SC) were not modified by b oldine at doses up to 40 mg/kg (IP) but were almost completely abolished by 40 mg/kg glaucine (IP). In the apomorphine-induced (0.1 mg/kg SC) rat yawn ing and penile erection model, boldine and glaucine appeared to be similarl y effective, inhibiting both behaviors by more than 50% at 40 mg/kg (IP). B oldine and glaucine, injected IP at doses up to 40 mg/kg, were poor modifie rs of dopamine metabolism in mouse and rat striatum. These data suggest tha t boldine does not display effective central dopaminergic antagonist activi ties in vivo in spite of its good binding affinity at D-1- and D-2-like rec eptors, and that glaucine, although less effective in vitro, does appear to exhibit some antidopaminergic properties in vivo. (C) 1998 Elsevier Scienc e Inc.