The effects of GABAA receptor blockade in the dorsomedial hypothalamic nucleus on corticotrophin (ACTH) and corticosterone secretion in male rats.
Experiments were conducted to test if blockade of GABAA receptors in the dorsomedial hypothalamic nucleus (DMH) of rats, which is known to elicit cardiovascular and anxiety responses, would also elicit changes in the plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone. Male Sprague-Dawley rats were anesthetized with pentobarbital, fitted with femoral arterial catheters and implanted with microinjection cannulae into the DMH or the sites anterior to the DMH (i.e., closer to the paraventricular nucleus (PVN) of the hypothalamus). The rats were then injected with either artificial cerebrospinal fluid (aCSF; 100 nl) or the GABAA antagonist, bicuculline methiodide (BMI; 50 pmol in 100 nl) and their plasma samples obtained at 5, 30, 60, and 120 min after microinjection. Plasma ACTH and corticosterone were measured by using a radioimmunoassay. Rats injected with BMI, but not aCSF, into the DMH showed significant increases in heart rate (HR, 110 +/- 16 beats/min), blood pressure (BP; 30 +/- 4 mmHg), and plasma levels of both ACTH (64 +/- 10 pg/ml) and corticosterone (170 +/- 25 ng/ml) from baseline. BMI injections into the anterior sites closer to the PVN did not elicit significant increases in HR, BP, or plasma levels of ACTH and corticosterone. These results suggest that a tonic GABAA receptor-mediated inhibition system regulates a coordinated physiological and neuroendocrine response in the DMH and that this neuroendocrine response is not due to diffusion of BMI to the PVN of rats.
Keim
S R
SR
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202, USA.
Shekhar
A
A
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006321:Heart / Q000187:drug effects; D007033:Hypothalamus, Middle / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone