GABA release from suprachiasmatic nucleus terminals is necessary for the light-induced inhibition of nocturnal melatonin release in the rat

The daily rhythm of melatonin production in the mammalian pineal is driven by the endogenous circadian pacemaker in the suprachiasmatic nuclei. The ma jor release period of melatonin is closely linked to the dark phase of the 24-h day/night cycle. Environmental light will affect melatonin release in two ways: (i) it entrains the rhythm of the circadian oscillator; and (ii) it causes an acute suppression of nocturnal melatonin release. These two ef fects of light are both mediated by the suprachiasmatic nucleus and enable the pineal gland to convey information about day length to the reproductive system through changes in melatonin levels. Glutamate is currently believe d to be the major transmitter in the retinal ganglion cell fibers reaching the suprachiasmatic nucleus. Ar present no information is available, howeve r, about the transmitter(s) implicated in the further propagation, i.e. fro m the suprachiasmatic nucleus onwards, of the light information. Ln the pre sent study we provide evidence that the endogenous release of GABA from sup rachiasmatic nucleus terminals is implicated in the further transmission of light information to the pineal gland. Bilateral administration of the GAB A-antagonist bicuculline to hypothalamic target areas of the suprachiasmati c nucleus completely prevents the inhibitory effect of nocturnal light on m elatonin secretion and the present study thus documents that retina-mediate d photic activation of suprachiasmatic nucleus neurons induces the release of GABA from efferent suprachiasmatic nucleus nerve terminals, resulting in an inhibition of melatonin release by the pineal gland. Together with our previous (electro)physiological data these results identi fy GABA as an important mediator of rapid synaptic transmission of suprachi asmatic nucleus output to its target areas. (C) 1999 IBRO. Published by Els evier Science Ltd.