Chronic treatment with the nitric oxide synthase inhibitor, L-NAME, attenuates estradiol-mediated improvement of learning and memory in ovariectomized rats

Abstract

INTRODUCTION:The role of ovarian hormones and nitric oxide in learning and memory has been widely investigated.OBJECTIVE:The present study was carried out to evaluate the effect of the nitric oxide synthase (NOS) inhibitor, N (G)-nitro-L-arginine methyl ester (L-NAME), on the ability of estradiol to improve learning in OVX rats using the Morris water maze.METHODS:Forty rats were divided into five groups: (1) ovariectomized (OVX), (2) ovariectomized-estradiol (OVX-Est), (3) ovariectomized-L-NAME 10 (OVX-LN 10), (4) ovariectomized-L-NAME 50 (OVX-LN 50) and (5) ovariectomized-estradiol-L-NAME 50 (OVX-Est-LN 50). The animals in the OVX-Est group were treated with a weekly injection of estradiol valerate (2 mg/kg; i.m.). The OVX-LN 10 and OVX-LN 50 groups were treated with daily injections of 10 and 50 mg/kg L-NAME (i.p.), respectively. The animals in the OVX-Est-LN 50 group received a weekly injection of estradiol valerate and a daily injection of 50 mg/kg L-NAME. After 8 weeks, all animals were tested in the Morris water maze.RESULTS:The animals in the OVX-Est group had a significantly lower latency in the maze than the OVX group (p<0.001). There was no significant difference in latency between the OVX-LN 10 and OVX-LN 50 groups in comparison with the OVX group. The latency in the OVX-Est-LN 50 group was significantly higher than that in the OVX-Est group (p<0.001).CONCLUSION:These results show that L-NAME treatment attenuated estradiol-mediated enhancement of spatial learning and memory in OVX rats, but it had no significant effect in OVX rats without estrogen, suggesting an interaction of nitric oxide and estradiol in these specific brain functions.

Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol

“…The results also showed that the animals of the OVX Group remembered the location of platform better than sham-operated ones. These results were in agreement with the previous studies 17,19 . In contrast with these findings, Herlitz et al showed that there were no considerable differences in cognitive performance between premenopausal and postmenopausal women 23 .…”

“…In contrast with these findings, Herlitz et al showed that there were no considerable differences in cognitive performance between premenopausal and postmenopausal women 23 . We have previously shown that administration of 2 mg/kg estradiol for eight weeks improved learning and memory in ovariectomized rats, but it had deleterious effect in sham-operated ones 18,19 . Therefore, the effect of chronically administering a higher dose of estradiol was examined in the present study.…”

“…OVX rats have been frequently used as a model of hormone deprivation to study postmenopausal changes in adult females [17][18][19] . The results showed that deletion of ovarian hormones impaired learning and memory in Morris water maze.…”

“…Then, it was removed from the pool, dried and placed in its holding bin for another 20 seconds. The time latency to reach the platform and the length of the swimming path were recorded by a video tracking system [17][18][19] .…”

“…It was previously shown that removal of ovaries impairs Morris water maze tasks which is reversible by L -arginine, the precursor of NO 17 . It was also shown that administration of 2 mg/kg estradiol valerate improved learning of OVX, but not sham-oprated rats using Morris water maze 18,19 . In the present study, the chronic effects of a higher dose of estradiol on learning, memory and NO metabolites in hippocampal tissues of OVX rats were investigated.…”