GABA Receptors in the Region of the Dorsomedial Hypothalamus of Rats Are Implicated in the Control of Melatonin and Corticosterone Release

Abstract

Recently, anatomical evidence was presented that the mammalian circadian clock located in the suprachiasmatic nuclei (SCN) may utilize GABA to transmit diurnal information to the dorsomedial hypothalamus (DMH). The present study provides further physiological evidence for the involvement of this GABAergic projection in the regulation of diurnal rhythms. Infusion of the GABA agonist muscimol in the region of the DMH completely blocked the daily increase of plasma melatonin during darkness and reduced sympathetic output in the pineal gland resulting in lower pineal melatonin production, as measured with transpineal microdialysis. Further experiments in SCN-lesioned animals indicated that the origin of this inhibitory input to the DMH is indeed the SCN. The results of this study imply that the SCN can influence the sympathetic outflow of the hypothalamus through its GABA-containing projection. Furthermore, the present results probably explain the previously reported strong inhibitory effect of benzodiazepines on plasma melatonin in both animals and humans.

Melatonin Suppression by Light in Humans Is Maximal When the Nasal Part of the Retina Is Illuminated

“…In rodents, the SCN are necessary for melatonin suppression by light to occur (Kalsbeek et al, 1996). If this holds for humans as well, then our finding implies that the human circadian pacemaker is differentially sensitive to light depending on the retinal area exposed.…”

“…Lesions of the SCN of rodents and sheep abolish the rhythmicity of melatonin secretion (Moore, 1993;Moore and Klein, 1974;Tessonneaud et al, 1995) but allow a basal melatonin synthesis to continue. Such lesions prevent the melatonin suppression response to light (Hastings and Herbert, 1986;Kalsbeek et al, 1996). Hence, it is possible to obtain functional information about the pathways from retina to SCN by investigating melatonin suppression in response to light.…”

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

“…PVN lesions abolish the rhythm of MEL synthesis in the pineal gland , PVN neurons respond to an electrical stimulation of SCN cells (Hermes et al, 1997), VIP or VP infusion in the PVN elevates pineal melatonin release (Kalsbeek et al, 1993), and retrograde labeling from the pineal gland is seen in the PVN (Larsen, 1999;Teclemariam-Mesbah et al, 1999). GABA appears to be involved in transmitting signals from the SCN to the PVN since infusion of a GABA antagonist during the subjective day in the PVN area stimulates MEL synthesis, whereas infusion of GABA during the night inhibits nighttime MEL secretion (Kalsbeek et al, 1996a(Kalsbeek et al, , 2000b. SCN lesions abolish the daily rhythm of MEL synthesis but keep MEL at a level intermediate between daytime and nighttime values.…”

Sympathetic input modulates, but does not determine, phase of peripheral circadian oscillators

“…Sympathetic efferent fibers responsible for these rhythms receive input from SCN neurons, which are entrained to the ambient light cycle via the retinohypothalamic tract (15). Moreover, there are many examples of light stimuli acutely affecting sympathetically controlled or regulated functions, presumably via sympathetic nerve activity [e.g., ambulatory heart rate (39,40), adrenal corticosterone secretion (5), pineal melatonin release (21)(22)(23), and salivary secretion (4)].…”