Effect of 6-hydroxydopamine on pineal norepinephrine content and enzyme activity in the cyclic female rat.

Abstract

The response of two pineal enzymes, serotonin N-acetyltransferase (SNAT; E.C.2.3.1.5) and hydroxyindole-O-methyltransferase (HIOMT; E.C.2.1.1.4) to the reduction of pineal norepinephrine (NE) content produced by systemic injections of 6-hydroxydopamine (6-OHDA) was examined in the present study twice daily, at 1200 and 2400 h, in the cyclic female rat. In rats sacrificed 3 days postinjection during the dark period (2400 h), injections of 6-OHDA that produced maximal inhibition of SNAT activity (58% of control values) also caused significant decreases in NE content in pineal, hypothalamic and cardiac tissues (48, 75 and 12% of control values, respectively). In rats sacrificed 17 days postinjection at 2400 h, SNAT activity and pineal NE content had returned to control levels, while hypothalamic and cardiac NE content remained significantly depressed (70 and 22% of control levels, respectively). These results confirm the role of NE in the induction of SNAT activity and reveal that 6-OHDA is more effective in decreasing cardiac than pineal NE content. In a second experiment, HIOMT activity was measured throughout the estrous cycle in both treated and control animals. Reduction of hypothalamic NE content by 6-OHDA did not block ovulation or disrupt the estrous cycle, although the initial cycle was prolonged by 1 day in some animals. Although average HIOMT activity during the estrous cycle in 6-OHDA treated animals did not differ from control levels, the amplitude of the circadian alteration in HIOMT activity as well as the relationship of this pineal enzyme to the estrous cycle was altered in animals receiving the drug. These findings suggest that the nocturnal rise in HIOMT activity and the relationship of this pineal enzyme to the estrous cycle are regulated, in part, by a NE sensitive component in either the pineal gland, hypothalamus or both.