CLOZAPINE AND OTHER NEUROLEPTIC DRUGS ANTAGONIZE THE LIGHT-EVOKED SUPPRESSION OF MELATONIN BIOSYNTHESIS IN CHICK RETINA - INVOLVEMENT OF THE D-4-LIKE DOPAMINE-RECEPTOR
Jb. Zawilska et al., CLOZAPINE AND OTHER NEUROLEPTIC DRUGS ANTAGONIZE THE LIGHT-EVOKED SUPPRESSION OF MELATONIN BIOSYNTHESIS IN CHICK RETINA - INVOLVEMENT OF THE D-4-LIKE DOPAMINE-RECEPTOR, Journal of neural transmission, 97(2), 1994, pp. 107-117
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.