title: Pharmacological modifications in dopaminergic neurotransmission affect the quinpirole-evoked suppression of serotonin N-acetyltransferase activity in chick retina: an impact on dopamine D4-like receptors.
abstract: 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 D4-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. ED50 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 ED50 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 D4-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.
authors.affiliation: Institute of Biogenic Amines, Polish Academy of Sciences, Lódź, Poland.
authors.forename: J B
authors.initials: JB
authors.lastname: Zawilska
authors.forename: T
authors.initials: T
authors.lastname: Derbiszewska
authors.forename: J Z
authors.initials: JZ
authors.lastname: Nowak
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D002645:Chickens; D002940:Circadian Rhythm / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D019257:Quinpirole / Q000494:pharmacology*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050638:Receptors, Dopamine D4; D012160:Retina / Q000187:drug effects / Q000201:enzymology; D012457:Salicylamides / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D050638:Receptors, Dopamine D4; D019257:Quinpirole; D020891:Raclopride; D007980:Levodopa; D013469:Sulpiride; D001191:Arylamine N-Acetyltransferase; D003024:Clozapine