GABA receptors in the posterior hypothalamus regulate experimental anxiety in rats.
Blockade of gamma-aminobutyric acid (GABA) function in the posterior hypothalamus of rats elicits a pattern of physiological and behavioral arousal consisting of increases in heart rate, respiration and blood pressure as well as intense locomotor stimulation and a selective enhancement of avoidance responding. The present study was conducted to assess the possibility that GABA-mediated neurotransmission in the posterior hypothalamus of the rat may regulate anxiety. Male rats were trained in a 'conflict' schedule consisting of a high and a low intensity of punishment ('high' and 'low' conflict) capable of measuring decreases and increases in the level of 'anxiety', respectively. Guide cannulae were stereotaxically implanted bilaterally in the posterior hypothalamus of these rats at sites where microinjection of bicuculline methiodide (BMI) 25 ng caused increases in heart rate under anesthesia. After recovery, they were tested: (1) in the high conflict schedule after microinjection of saline and two doses of the GABAA receptor agonist muscimol; and (2) in the low conflict schedule after injecting saline, the GABAA receptor antagonists, BMI and picrotoxin, and the glycine antagonist, strychnine. Injection of muscimol caused a significant and selective anti-conflict effect while both BMI and, at appropriate doses, picrotoxin produced pro-conflict effects. Microinjection of strychnine into the posterior hypothalamus or muscimol and picrotoxin into the lateral hypothalamus did not influence conflict responding. These results suggest that endogenous GABA acts on GABAA receptors in a discrete area of the posterior hypothalamus to regulate the level of experimental anxiety in rats.
Shekhar
A
A
Department of Pharmacology, Indiana University School of Medicine, Indianapolis 46202.
Hingtgen
J N
JN
DiMicco
J A
JA
D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D001640:Bicuculline / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism*; D007034:Hypothalamus, Posterior / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D001640:Bicuculline; D010852:Picrotoxin; D011963:Receptors, GABA-A