MK-801 affects cardiovascular responses produced by GABAA agents in area postrema.
The cardiovascular effects of nanoliter microinfusions of muscimol, bicuculline, and MK-801 (dizocilpine) into area postrema (AP) were tested in urethane-anesthetized male Sprague-Dawley rats. Microinfusion of muscimol (10 nl/min/5min, 1 ng/nl) into the AP produced significant hypertension (+29 +/- 8 mmHg), but no significant change in heart rate (HR). Microinfusion of bicuculline (10 nl/min/5 min, 1 ng/nl) into the AP produced significant hypotension (-27 +/- 4 mmHg) and bradycardia (-53 +/- 10 bpm). Treatment of the AP with MK-801 (20 nl/min/5 min, 6 ng/nl) produced no changes in mean arterial pressure or HR by itself, but it completely blocked the hypotension and bradycardia produced by bicuculline infusion, without affecting the hypertension produced by muscimol microinfusion into AP. Following pretreatment of AP with MK-801, microinfusion of muscimol into the AP produced significant tachycardia (+51 +/- 16 bpm). The data suggest that a) GABAergic neurotransmission in the AP affects its cardiovascular functions; b) functional interactions between NMDA receptor-mediated neurotransmission and GABAA receptor-mediated neurotransmission within the AP modulate blood pressure and HR regulation.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens 30602.
B
B
Tian
D K
DK
Hartle
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects*; D007263:Infusions, Parenteral; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D016291:Dizocilpine Maleate; D001640:Bicuculline