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 entoped uncular 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.