Age-related changes in the diurnal rhythm of serotonin turnover in microdissected brain areas of estradiol-treated ovariectomized rats

The purpose of this study was to determine whether 1) a diurnal rhythm in serotonin turnover is present in specific hypothalamic nuclei of middle-aged ovariectomized rats and 2) in middle-aged animals exposure to estrogen can induce the pattern of serotonin dynamics which appears necessary for the occurrence of an LH surge in young rats. Young (3-4 month old) and middle-aged (8-10 month old) rats which demonstrated estrous cyclicity were bilaterally ovariectomized. Seven days later half of the young and middle-aged animals received Silastic estradiol capsules. On day 9 post ovariectomy the groups were again divided; half of the rats in each group were killed at 0800, 1200, 1800, and 2400 h. Remaining animals were treated with pargyline (75 mg/kg BW, ip) at these times and were killed 10 min later, and the following brain areas were microdissected and analyzed for serotonin (5HT) and 5-hydroxyindole acetic acid: median eminence (ME), suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), arcuate nucleus (AN), and globus pallidus. In young ovariectomized rats the SCN, MPN, and AN exhibited a diurnal rhythm in 5HT activity which was high during the light hours and low during the dark. The diurnal rhythm could not be detected in any hypothalamic nuclei of ovariectomized middle-aged animals. The loss in the circadian component of 5HT activity is not due to a loss in serotonergic function, since overall turnover rates were not reduced compared to young animals. Estrogen treatment modified the diurnal pattern of 5HT activity in the SCN, MPN, and AN in young rats but had no effect in the middle-aged rats. In young rats, estrogen induced a transitory rise in ME-5HT turnover at 1200 h, just before the expected onset of the LH surge. In middleaged animals the increase in ME-5HT turnover did not occur until 1800 h and correlates with a delay in the initiation of the estradiol-induced LH surge. We conclude that: 1) there is a loss in the rhythm of 5HT activity in middle-aged rats and 2) the diurnal rhythmicity of 5HT turnover may be necessary for the maintenance of normal cyclic release of LH.