Alpha and beta noradrenergic mediation of NMDA glutamatergic effects on lordosis behaviour and plasmatic LH concentrations in the primed female rat.
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.
Landa
Adriana Inés
AI
Laboratorio de Neurociencias y Psicología Experimental, Area de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU-CONICET), Mendoza, Argentina.
Gargiulo
Angel José Martín
AJ
Gargiulo
Mercedes María Lucrecia
MM
Cabrera
Ricardo Jorge
RJ
Bregonzio
Claudia
C
Lafuente Sánchez
José Vicente
JV
Gargiulo
Pascual Angel
PA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003307:Copulation / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018690:Excitatory Amino Acid Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007986:Luteinizing Hormone; D009638:Norepinephrine