Postsynaptic dopamine (DA) receptor stimulator properties of the putative DA autoreceptor-selective agonist B-HT 920 uncovered by co-treatment with the D-1 agonist SK&F 38393

Abstract

Postsynaptic dopaminergic behavioural effects of D-2 agonists can be promoted by concomitant D-1 receptor activation. The present experiment explored whether such effects could be elicited by the putative autoreceptor-selective D-2 agonist B-HT 920, when combined with the D-1 agonist SK&F 38393. Except for occasional jerks induced by B-HT 920, neither agonist caused significant dopaminergic stimulation when given separately, whereas combined treatment with SK&F 38393 and B-HT 920 induced clear-cut motor activation--particularly focused stereotyped licking and sniffing--in reserpine/AMT-pretreated rats. Both the D-1 antagonist SCH 23390 and the D-2 antagonist spiperone abolished these effects, while the SK&F/B-HT-induced stimulation was not significantly affected by the alpha 2-blocker idazoxan. It appears that classical postsynaptic DA receptor-stimulatory properties of B-HT 920 can indeed be demonstrated, provided that sufficient D-1 receptor tone prevails.