Dopamine D1 Receptor Agonist SKF Research Articles

BHT 920 stimulates postsynaptic D2 dopamine receptors in the normal rat: Electrophysiological and behavioral evidence

The putative autoreceptor-selective dopamine (DA) agonist B-HT 920 was tested using electrophysiological and behavioral models thought to reflect actions at postsynaptic D2 DA receptors. Direct iontophoretic application of B-HT 920 onto nucleus accumbens neurons caused a current-dependent inhibition of firing which could be attenuated by pretreatment with α-methyl-p-tyrosine (to deplete DA) and reinstated (enable) by concurrent administration of the selective D1 DA receptor agonist SKF 38393. These findings suggest that, like other selective D2 DA receptor agonists, the postsynaptic effects of B-HT 920 require concurrent stimulation of D1 DA receptors. Behavioral indices of postsynaptic D2 DA receptor stimulation (stereotyped sniffing and rearing) were also evident following combined treatment with B-HT 920 and SKF 38393. Moreover, similar “low-level” stereotyped behaviors were also observed when B-HT 920 was administered alone following pretreatment with the α-2 adrenoceptor antagonists idazoxane and piperoxane, suggesting that α-2 agonist actions of B-HT 920, in some way, mask the expression of D2 receptor-mediated stereotyped responses. When B-HT 920 was combined with SKF 38393 following pretreatment with idazoxane, both the intensity and form (continual licking and gnawing) of stereotyped behavior was enhanced. Taken together, these electrophysiological and behavioral findings indicate that B-HT 920 possesses the properties of a selective D2 DA receptor agonist and cannot be considered as a DA autoreceptor-selective compound.

Coupling of dopamine D1 recognition sites with adenylate cyclase in nuclei accumbens and caudatus of schizophrenics.

Sodium fluoride, guanylimidodiphosphate, and the D1 dopamine receptor agonist SKF 38393 elicited a greater activation of adenylate cyclase in homogenates of caudate nucleus in schizophrenic than in nonschizophrenic subjects used as controls. Similarly, a greater activation of adenylate cyclase by sodium fluoride was observed in the nucleus accumbens of schizophrenics. These findings suggest that the coupling of dopamine D1 recognition sites with adenylate cyclase is more efficient in the brain of the schizophrenic, presumably because of an increased affinity of the G/F protein for guanosine 5'-triphosphate.