Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat

Abstract

We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogenprimed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogenprimed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an α1-and α2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 µg/6 µL) prior to NMDA administration (1 µg/2 µL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 ± 3.28, N = 28) when compared to saline controls (6 and 2 µL, 16.59 ± 3.20, N = 27) was abolished by prazosin administration (17.04 ± 5.52, N = 17, and 9.33 ± 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 ± 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 ± 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the α-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by α-noradrenergic transmission.

Alpha and beta noradrenergic mediation of NMDA glutamatergic effects on lordosis behaviour and plasmatic LH concentrations in the primed female rat

“…Two stud males (300-400 g) were introduced into the arena at least 10 min before the female was placed. As in previous studies (Landa et al 2006), the behavioral tests ended when the test female had received 30 male copulatory acts or after 15 min.…”

“…The aim of the present experiment was to study the interaction between glutamatergic and noradrenergic transmission in this model. Sexual behavior was correlated with luteinizing hormone (LH) release in the same experimental animals, as it was done in our previous studies (Gargiulo et al 1992;Gargiulo and Donoso 1995;Landa et al 2006).…”

“…The role of a-1-adrenoreceptors mediating facilitatory effects of the catecholamine neurotransmitter norepinephrine on both lordosis behavior and LH release has been extensively postulated (Etgen 2003). In a previous study, we have observed that prazosin, a specific non-selective a-adrenergic antagonist, decrease the lordosis behavior and luteinizing hormone secretion in the estrogen primed female rat (Landa et al 2006). Aiming to study the possible a-1 and b-adrenoreceptor mediation of NMDA effects we used two antagonists.…”

Anxiolytic-like effects of Atenolol injected into the nucleus accumbens septi in rats after restrain stress in the elevated plus maze test

“…As an alternative strategy, antagonism of secondary neurons activated by glutamate could be attempted. We have previously shown that noradrenergic blockade antagonizes some effects of glutamatergic stimulation on behavioural and endocrine parameters (Landa et al, 2006;Landa et al, 2009). It allows thinking that noradrenergic antagonism may mimic the anxiolytic effect of glutamate antagonists.…”