Selective enhancement of shock avoidance responding elicited by GABA blockade in the posterior hypothalamus of rats.
Recent studies have shown that blockade of gamma-aminobutyric acid (GABA) in the posterior hypothalamus in anesthetized rats elicits cardio-respiratory stimulation similar to that seen in emotional defense reactions and, in conscious rats, locomotor arousal suggesting a flight response. The present study was conducted in order to test the hypothesis that the behavioral effects elicited by GABA blockade in the posterior hypothalamus were the results of disinhibiting a mechanism whose activation selectively enhances reactivity to aversive stimuli. Male rats were trained on a Sidman shock avoidance schedule (RS20:SS10) as well as a food-reinforced approach schedule (VI 1). Under anesthesia, guide cannulae were stereotaxically implanted bilaterally in the posterior hypothalamus at sites where microinjection of the GABA antagonist, bicuculline methiodide (BMI) 25 ng, increased heart rate. After recovery, rats were tested in both the avoidance and VI 1 schedules after hypothalamic microinjection of saline, BMI 25 ng, and the GABA agonist, muscimol 25 ng. Microinjection of BMI significantly increased the avoidance responses but had no effect on the approach responses. Muscimol decreased both the avoidance and approach responses. When microinjected into the lateral hypothalamic area, BMI had no effect on the response rates in either schedule while muscimol decreased the approach responding only. Therefore, GABA blockade at the discrete area of the posterior hypothalamic nucleus appears to elicit a selective enhancement of avoidance responses. These results suggest that an endogenous GABAergic system in the posterior hypothalamus may tonically inhibit a constellation of autonomic, locomotor and motivational responses that are necessary for some types of defense reaction.
Shekhar
A
A
Department of Pharmacology, Indiana University School of Medicine, Indianapolis 46223.
Hingtgen
J N
JN
DiMicco
J A
JA
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D004597:Electroshock; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000502:physiology*; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013331:Strychnine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009118:Muscimol; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D013331:Strychnine; D001640:Bicuculline