Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes.
Push-pull superfusion was used to investigate the release of endogenous GABA in the posterior hypothalamus of the conscious, freely moving rat at basal conditions and in response to centrally applied drugs or to peripherally induced blood pressure changes. After an initial, exponential decline, the release rate of GABA remained fairly constant for many hours. Fluctuations in the release rate of GABA point to the existence of an ultradian rhythm with an approximate frequency of 1 cycle/65 min. Hypothalamic superfusion with a potassium-rich (50 or 90 mmol/l) artificial cerebrospinal fluid led to a concentration-dependent increase in the GABA release. The release of GABA was also enhanced by veratridine (1 or 10 mumol/l) in a concentration-dependent way. Hypothalamic superfusion with the neutrotoxin tetrodotoxin (1 mumol/l) led to a long-lasting decrease in the GABA release. The rise in blood pressure (45 mmHg) elicited by an intravenous infusion of noradrenaline was associated with an increased release rate of GABA in the hypothalamus. Hypotension produced by nitroprusside (25 mmHg) led to a counteracting decrease in hypothalamic GABA outflow. The findings suggest that approximately 45% of the basal outflow of GABA found in the superfusate are released from GABA-ergic neurons of the posterior hypothalamus. The release rate of GABA fluctuates according to an ultradian rhythm. The modified release of GABA in response to experimentally induced blood pressure changes suggests that, in the posterior hypothalamus of the conscious rat, GABAergic neurons are involved in cardiovascular control and possess a hypotensive function.
Institut für Pharmakologie und Toxikologie, Universität Innsbruck, Austria.
N
N
Singewald
L
L
Guo
A
A
Philippu
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002404:Catheterization / Q000379:methods; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000378:metabolism*; D007263:Infusions, Parenteral; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*
D009599:Nitroprusside; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D014701:Veratridine; D009638:Norepinephrine