Effects of kappa receptor agonists on D1 and D2 dopamine agonist and antagonist-induced behaviors

Abstract

Striatal dynorphin-containing neurons receive dopaminergic inputs from the substantia nigra pars compacta and project primarily to the substantia nigra pars reticulata and entopeduncular nucleus. These neurons mainly express dopamine (DA) D1 receptors and thus dynorphin system stimulation might be expected largely to influence D1 receptor agonist or antagonist effects on motor function. It is well known the interaction existing between DA D1 and D2 drugs in the induction of behavioral effects. However, the effects of dynorphin on selective D1 and D2 DA agonist and antagonist-induced behaviors have not yet been investigated. Administration of the kappa agonists spiradoline (0.5, 1 and 5 mg/kg) or U50,488H (1, 10 and 25 mg/kg) decreased non-stereotyped grooming induced by the selective D1 agonist SKF38393. This effect was inhibited by the non-selective opioid receptor antagonist naloxone (20 mg/kg) and by the selective kappa antagonist nor-binaltorphimine (nor-BNI, 20 mg/kg). Stereotypies induced by the selective D2 agonist quinpirole were decreased by spiradoline (1 and 5 mg/kg) and by U50,488H (1, 10 and 25 mg/kg), while jerking movements of a type associated with increased D2 receptor and decreased D1 receptor stimulation emerged. Kappa agonist effects were inhibited by the prior administration of SKF38393 (10 mg/kg); these inhibitory effects were blocked by prior administration of the D1 antagonist SCH23390 (5 mg/kg). Naloxone reversed the effects of both kappa agonists on quinpirole-induced stereotypies. Kappa agonists increased D1 antagonist-induced catalepsy, but had no effect on D2 antagonist-induced catalepsy. Naloxone and nor-BNI inhibited this effect. These results suggest that the motoric effects of D1 receptor antagonists in part reflect stimulation of striatal dynorphin containing efferents.