Pharmacological modifications in dopaminergic neurotransmission affect the quinpirole-evoked suppression of serotonin N-acetyltransferase activity in chick retina: An impact on dopamine D-4-like receptors

Dopamine (DA) plays an important role in the regulation of melatonin biosynthesis in retinas of several vertebrate species. In the retina of chick, the DA receptor controlling melatonin production represents a D-4-like subtype. Stimulation of this receptor by quinpirole (QNP) results in a dose-dependent decline of the nighttime activity of serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthesis) and melatonin level of chick retina. The present study was undertaken to determine whether long-term treatment with antipsychotic drugs (clozapine - 30 mg/kg, i.m.; sulpiride - 100 mg/kg, i.m.; and raclopride - 10 mg/kg, i.p., once daily for 21 days) and L-DOPA (80 mg/kg, i.p., once daily for 7 days) affects the response of the melatonin generating system of chick retina to the suppressive effect of QNP. Chronic administration to chicks of clozapine and sulpiride, but not raclopride, resulted in a markedly increased response of retinal NAT activity to the action of QNP. ED(50) values for QNP were 3-times (clozapine) and 4-times (sulpiride) lower than those in the respective vehicle-treated control groups. On the other hand, QNP was significantly less potent in retinas of birds treated with L-DOPA than in control animals; the ED(50) value for QNP was 3-times higher in birds injected with L-DOPA than in the vehicle-treated group. These results indicate that long-term treatment with clozapine, sulpiride and L-DOPA may modify the reactivity of D-4-like DA receptors regulating NAT activity of chick retina. A possibility of modifications of circadian and electrophysiological processes within the eye following prolonged administration of DA-ergic drugs is discussed.