Uptake of serotonin and norepinephrine in hypothalamic and limbic brain regions during the estrous cycle and the effect of neurotoxin lesions on estrous cyclicity.

The temporal pattern of hypothalamic and limbic aminergic activity during the estrous cycle has been measured by changes in the serotonergic and noradrenergic neuronal uptake during the regular estrous cycle. Significant changes (p = 0.006, 0.01) in the uptake of 3H 5-HT and 3H NE were recorded in the suprachiasmatic nuclei (SCN) at 1200 hours on proestrus. Significant changes (p = 0.01, 0.018) in the uptake of 3H 5-HT in the preoptic area (POA) were found at 1200 hours on both diestrus and proestrus while median eminence (ME) 5-HT showed a significant increase only during proestrus (p = 0.001). In the amygdala (AMYG) 3H 5-HT uptake was significantly different at 1200 hours on diestrus and proestrus while 3H NE uptake was significant (p = 0.001) at 1200 hours only during proestrus. The plasma proestrous luteinizing hormone surge occurred at 1700 hours. The serotonin neurotoxin, 5,7-dihydroxytryptamine, was stereotaxically injected through a 30 gauge needle in concentrations of 5-10 micrograms/microliters/minute for 1 minute in various nuclear regions. In the SCN 4 or 5 day estrous cyclicity was interrupted by diestrus for average periods of up to 15 days; in the POA for periods of 10 days; in the ME for periods of 13 days; and in the AMYG for periods of up to 6 days. Sham injections of 5% ascorbic acid had no effect on cyclicity and following these periods of acyclicity rats resumed normal cycles. These lesion effects and patterns of uptake suggest a common timing mechanism utilizing serotonergic raphe systems for neuroendocrine control. Lesions with 5,7-DHT in all four brain regions disrupt cyclicity, but the greatest delays occur in the SCN and ME regions which are particularly critical to intrinsic neuroendocrine rhythms. Patterns of increase in reuptake capacity in all 4 regions occur 3 hours prior to the critical period for the plasma LH surge and may be an important mechanism for many types of neuroendocrine events including ovulation.