Interactions of endogenous opioid and excitatory amino acid inputs to the caudal ventrolateral medulla of the rat.
This study investigated the cardiovascular consequences of interactions between endogenous opioid and excitatory amino acid inputs to the caudal ventrolateral medulla of the anaesthetised rat. Drugs were injected bilaterally into the functionally identified depressor region of the caudal ventrolateral medulla. The opioid antagonist, naloxone (2.5-8.0 nmol/side) elicited a dose-dependent decrease in blood pressure and a bradycardia. The NMDA-receptor antagonist, 2-amino, 5-phosphonovaleric acid (2-APV; 1.25-500 pmol/side), dose-dependently increased blood pressure but had little effect on heart rate. After the maximum dose of naloxone, the pressor response to both 1.25 and 25 pmol/side of 2-APV was attenuated by 89 and 66%, respectively. By contrast, the pressor response, elicited by injection of the GABA agonist, muscimol (1 pmol/side), was not affected. After 2-APV (500 pmol/side), the depressor response to 2.5 nmol/side of naloxone was enhanced by 84%, although this effect was lost when a larger dose of naloxone (5 nmol/side) was used. 2-Amino,5-phosphonovaleric acid also potentiated the depressor response to a submaximal dose of the GABA antagonist, bicuculline (2 pmol/side). The results suggest firstly that, in the caudal ventrolateral medulla, excitatory amino acid inputs are functionally less important when tonic opioid effects are blocked. This interaction appears to be pharmacologically specific. Secondly, tonic inhibitory inputs, whether due to opioids or to GABA, are functionally more effective after excitatory amino acid inputs are antagonized.
Department of Medicine, Flinders University, Bedford Park, South Australia.
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E
Badoer
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J
Chalmers
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007267:Injections; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY
D000596:Amino Acids; D004723:Endorphins; D009118:Muscimol; D009270:Naloxone; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline