SIGMA-RECEPTOR MODULATION OF NORADRENERGIC-STIMULATED PINEAL MELATONIN BIOSYNTHESIS IN RATS

Because sigma receptors are richly concentrated in the rat pineal glan d, the present study was performed to investigate their possible role in the modulation of melatonin production. To this purpose, we assesse d in vivo the effects of the sigma-receptor ligands 1,3-di(2-tolyl) gu anidine and (+)-N-allylnormetazocine on the rat pineal gland activity during either the daytime or the nighttime. Compared with vehicle, 1,3 -di (2-tolyl)guanidine and (+)-N-allylnormetazocine potentiated the en hancement of N-acetyltransferase activity and pineal melatonin content induced by isoproterenol administration during the daytime, whereas t hey did not affect the diurnal basal biosynthetic activity of the glan d. Conversely, at night, 1,3-di(2-tolyl)guanidine and (+)-N-allylnorme tazocine enhanced significantly the physiological increases in both pi neal N-acetyltransferase activity and melatonin levels. This enhanceme nt was prevented by pretreatment with rimcazole, a specific sigma-rece ptor antagonist. These findings suggest that, in rats, the activation of pineal sigma-receptor sites does not affect the biosynthetic activi ty of the pineal gland during daytime, whereas it pontentiates the pro duction of melatonin when the gland is noradrenergically stimulated ei ther by isoproterenol administration or by the endogenously released n orepinephrine at nighttime.