No abstract

In previous studies we have found that blockade of NMDA (N-Methyl-D-Aspartic-Acid)-type glutamatergic receptor with intracerebroventricular (ICV) selective drugs induces an inhibition of lordosis in ovariectomized (OVX) estrogen primed rats receiving progesterone or luteinizing hormone releasing hormone (LHRH). By the opposite way, stimulation with NMDA in OVX estrogen primed rats induced a significant increase of lordosis. In the present study the action of an alpha1-noradrenergic antagonist, HEAT (BE 2254/2-beta-4-Hydroxyphenyl-Ethyl-Aminomethyl-1-Tetralone), and Metoprolol, a beta-noradrenergic antagonist, were studied injecting them ICV previously to NMDA administration in treated OVX estrogen primed rats. In experiment 1, the enhancing effect on lordosis induced by NMDA at high dose (1 microg) was abolished by HEAT administration (P < 0.001 for 3 and 6 microg), and the LH plasma levels were decreased only with the higher dose (P < 0.05), suggesting that behavioral effects are quite more sensitive to the alpha-blockade than hormonal effects. In experiment 2, enhancing effects on lordosis behavior were not observed with neither the NMDA at low dose (0.5 microg) nor the metoprolol alone (5.71 microg), but a synergism was observed when both were simultaneously administered (P < 0.001). The LH plasma levels were increased by Metoprolol alone (P < 0.05), and powered by the combination with NMDA at low dose (P < 0.01 vs. SAL and NMDA alone); no differences were observed with Metoprolol. LH increase was observed with Metoprolol even without behavioural modifications. These findings strongly suggest that facilitatory and inhibitory effects of NMDA in this model are mediated by alpha- and beta-adrenergic transmission in both, behavioral and hormonal effects.

<b><i>Introduction:</i></b> In recent years, an important number of studies have emphasized the psychopharmacological actions of cycloleucine (1-aminocyclopentanecarboxylic acid) acting on the NR1 subunit (glycine allosteric site) of NMDA (N-methyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. <b><i>Methods:</i></b> The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1 µL injections of saline or cycloleucine (0.5, 1, 2, or 4 µg) 15 min before testing. <b><i>Results:</i></b> Time spent in the open arm was significantly increased by cycloleucine treatment with all doses (1 and 2 µg, <i>p</i> &#x3c; 0.05; 0.5 and 4 µg, <i>p</i> &#x3c; 0.01), like number of extreme arrivals (0.5 and 1 µg, <i>p</i> &#x3c; 0.05; 2 µg, <i>p</i> &#x3c; 0.01; and 4 µg, <i>p</i> &#x3c; 0.001). Open arm entries were increased by the highest dose only (4 µg, <i>p</i> &#x3c; 0.01). <b><i>Discussion/Conclusion:</i></b> Present results show no difference between all doses in the time spent in the open arm, suggesting an indirect, noncompetitive action of the drug. The increase in extreme arrivals and open arm entries suggests a dose influence in these parameters. We conclude that cycloleucine influence on the NMDA receptors within NAS leads to anxiolytic-like effects and behavioral disinhibition, which once more confirms the involvement of NAS in anxiety processing.

We conclude that dizocilpine-glutamatergic blockade in the accumbens lead to an anxiolytic-like effect and a behavioral disinhibition related to an increase in some motoric parameters, showing specific behavioral patterns.