The adrenal medulla may mediate the increase in pineal melatonin synthesis induced by stress, but not that caused by exposure to darkness.

As previously shown (Lynch et al.: Proc. Nat. Acad. Sci. [U.S.A.] 70, 1704-1707 [1973]), the activity of the enzyme serotonin-N-acetyltransferase (NAT) in the rat pineal increases when the animal is placed in darkness or is subjected to the stress of physical immobilization; partial sympathetic denervation (i.e., pretreatment of the animal with intravenous 6-hydroxydopamine [6-OHDA]) does not block either response. The present studies explored the roles of the pineal sympathetic nerves and the adrenal medullas in mediating these responses. The stress-induced increase in pineal NAT activity was blocked by bilateral adrenalectomy, but not by bilateral superior cervical ganglionectomy or by treatment with 6-OHDA (both of which potentiate the NAT response in normal rats and restore it in adrenalectomized ones). The increase in pineal melatonin content caused by immobilization was also blocked by adrenalectomy, but potentiated by pineal sympathetic denervation. In contrast, bilateral adrenalectomy did not affect the darkness-induced rise in pineal NAT activity, although pineal sympathetic denervation (by bilateral superior cervical ganglionectomy) did block this response. 6-OHDA pretreatment neither blocked the response to darkness nor restored it in ganglionectomized animals; thus, this treatment apparently fails to produce a complete pineal denervation. The pineal response to stress has previously been shown to be blocked by beta-adrenergic blocking agents. The present studies demonstrate that alpha-adrenergic blockade (with phenoxybenzamine) potentiates this response in intact animals and restores it in adrenalectomized rats (possibly by acting presynaptically on receptors on pineal sympathetic terminals and thereby augmenting norepinephrine release). These observations show that the rat pineal organ normally receives information from two "channels", i.e., trans-synaptically (from pineal sympathetic nerves) and via the circulation (from the adrenal medullas and, perhaps, from distant sympathetic nerves).