CLOZAPINE AND OTHER NEUROLEPTIC DRUGS ANTAGONIZE THE LIGHT-EVOKED SUPPRESSION OF MELATONIN BIOSYNTHESIS IN CHICK RETINA - INVOLVEMENT OF THE D-4-LIKE DOPAMINE-RECEPTOR

The subtype of dopamine receptor mediating the suppressive effect of l ight on melatonin biosynthesis in chick retina was characterized pharm acologically. Acute exposure of animals to light during the dark phase of the light-dark cycle dramatically decreased melatonin levels and a ctivity of serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthetic pathway). Various antagonists of dopamine r eceptors were tested for their ability to block this action of light o n the retinal melatonin formation. Intraocular (i. oc.) pretreatment o f chicks with neuroleptic drugs - blockers of the D-2-family of dopami ne receptors, i.e., clotiapine, clozapine (an atypical neuroleptic wit h high affinity for a D-4-subtype dopamine receptor), haloperidol, spi roperidol, sulpiride, and YM-09151-2, significantly antagonized the li ght-evoked suppression of the nighttime NAT activity of the chick reti na in a dose-dependent manner. In contrast, remoxipride (a D-2-selecti ve dopamine antagonist), raclopride and(+)-UH-232 (D-2/D-3-dopamine re ceptor antagonists), as well as SCH 23390, a blocker of the D-1-family of dopamine receptors, were ineffective. Clozapine, haloperidol, spir operidol and sulpiride also potently antagonized the suppressive actio n of light on melatonin content of the chick retina. It is suggested t hat the dopamine receptor mediating the inhibitory effect of light sti mulation on the nighttime melatonin biosynthesis in the retina of chic k represents a D-4-like subtype.