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 b iosynthesis 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) res ults in a dose-dependent decline of the nighttime activity of serotoni n N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosy nthesis) and melatonin level of chick retina. The present study was un dertaken to determine whether long-term treatment with antipsychotic d rugs (clozapine - 30 mg/kg, i.m.; sulpiride - 100 mg/kg, i.m.; and rac lopride - 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 g enerating system of chick retina to the suppressive effect of QNP. Chr onic administration to chicks of clozapine and sulpiride, but not racl opride, resulted in a markedly increased response of retinal NAT activ ity to the action of QNP. ED(50) values for QNP were 3-times (clozapin e) 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 l ong-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 electrophysiol ogical processes within the eye following prolonged administration of DA-ergic drugs is discussed.