Role of norepinephrine in the dorsomedial hypothalamic panic response: an in vivo microdialysis study.
Blockade of gamma-aminobutyric acid-A (GABA(A)) receptors in the dorsomedial hypothalamus (DMH) elicits a panic-like response that includes increases in heart rate (HR), blood pressure (BP), respiration rate (RR), and anxiety. Norepinephrine (NE) has been postulated to be critical in regulating panic and anxiety responses. Therefore, the first study sought to determine changes in extracellular NE levels within the DMH following acute blockade of GABA(A) receptors in the DMH using in vivo microdialysis. Rats were implanted with femoral arterial catheters and microdialysis probes into the DMH. Following recovery, the DMH of conscious rats were perfused with 100, 150, or 200 microM solutions of the GABA(A) receptor antagonist bicuculline methiodide (BMI) via the microdialysis probe. HR and BP responses were recorded and the changes in extracellular levels of NE in the dialysate samples from the DMH were determined by HPLC. Rats receiving BMI injections showed dose-dependent increases in both the extracellular NE levels in the DMH as well as HR and BP. The second study was conducted to test the functional importance of NE in the DMH to the BMI-induced physiological responses. The effects of BMI microinjection into the DMH were measured at baseline and 10 days after local injection of either vehicle or two doses of 6-hydroxydopamine (6-OHDA), a neurotoxin known to lesion NE terminals. There was a significant loss of tissue NE levels as well as BMI-induced HR, BP and RR responses in the 6-OHDA-treated but not vehicle-treated rats. Thus, blockade of GABA(A) receptors in the DMH results in NE release and the presence of NE appears to be necessary for eliciting the physiological components of the panic-like responses in this region.
Shekhar
A
A
Department of Psychiatry, Institute of Psychiatric Research, Indiana University Medical Center, Indianapolis, IN 46202, USA. ashekhar@iupui.edu
Katner
J S
JS
Sajdyk
T J
TJ
Kohl
R R
RR
D018663:Adrenergic Agents; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine; D010200:Panic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism
D018663:Adrenergic Agents; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D016627:Oxidopamine; D009638:Norepinephrine