Aging alters norepinephrine release in the medial preoptic area in response to steroid priming in ovariectomized rats

Changes in luteinizing hormone (LH) secretion that are observed in aging animals have been attributed to a reduction in hypothalamic norepinephrine (NE). The reason for the reduction in NE levels with aging is unclear. We hypothesized that the responsiveness of noradrenergic neurons to ovarian steroids is altered during aging. To test this, regularly cycling female Sprague-Dawley rats (young: 4-5 months old and middle age: 8-11 months old) were implanted with a push-pull cannula in the medial preoptic area (MPA) and ovariectomized bilaterally. On the 8th day after ovariectomy, they were injected with estrogen (30 microg/100 microl corn oil, s.c.) at 1000 h and on the 9th day they were implanted with a jugular catheter. On the 10th day they were injected with progesterone (2 mg/100 microl corn oil, s.c.) at 1000 h and subjected to push-pull perfusion. Perfusate samples from the MPA were collected at the rate of 10 microl/min every 30 min from 1300 to 1800 h and blood samples (0.3 ml) were collected hourly. The perfusate samples were analyzed for NE and dopamine (DA) concentrations using high performance liquid chromatography with electrochemical detection and serum LH levels were determined by RIA. In young animals, NE release (mean+/-S.E., pg/min) was 4.0+/-1.1 pg/min at 1300 h and increased significantly (p<0.05) to 10.4+/-4.3 pg/min at 1500 h and remained elevated until 1600 h and then declined to 6.8+/-2.5 at 1730 h. In contrast, the increase in NE release occurred briefly in middle-aged animals and was delayed by an hour. LH patterns in both age groups followed the pattern in NE release. There was no change in the release of DA in both young and middle-aged animals. It is concluded that the altered responsiveness of noradrenergic neurons to steroid priming in middle-aged rats probably plays a critical role in the alterations seen in LH secretion in older animals.