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Previous Article | Next Article
Volume 17, Number 24, Issue of December 15, 1997 pp. 9726-9735
The Circumventricular Organs Form a Potential Neural Pathway for Lactate Sensitivity: Implications for Panic Disorder
Received April 11, 1997; revised Sept. 24, 1997; accepted Sept. 29, 1997.
Anantha Shekhar and Stanley R. Keim Departments of Psychiatry and Pharmacology and Toxicology, Indiana University Medical Center, Indianapolis, Indiana 46202
Patients with panic disorder experience panic attacks after intravenous sodium lactate infusions by an as yet unexplained mechanism. Lactate elicits a panic-like response in rats with chronic dysfunction of GABA neurotransmission in the dorsomedial hypothalamus (DMH). The circumventricular organs, organum vasculosum lamina terminalis (OVLT) and subfornical organ (SFO), are potential sites that could detect increases in plasma lactate levels and activate the DMH. To test this, we obtained baseline heart rate (HR) and blood pressure (BP) responses to lactate infusions in rats fit with femoral arterial and venous catheters. Next, unilateral chronic injection cannulae connected to an Alzet infusion pump filled with the GABA synthesis inhibitor L-allylglycine (L-AG) were implanted into the DMH. Another chronic injection cannula was implanted into the region of the OVLT, SFO, or an adjacent control site, the median preoptic area (MePOA). These rats were tested once again with lactate infusions after injection of either artificial cerebrospinal fluid (ACSF) or tetrodotoxin (TTX) into the CVO sites. Injecting TTX into the OVLT completely blocked the lactate-induced response, whereas TTX injections into the SFO or MePOA did not. Also, direct injections of lactate (100 or 500 nl) into the OVLT elicited robust anxiety-like responses in these rats. These results suggest that the OVLT may be the primary site that detects lactate infusions, activating an anxiety-like response in a compromised DMH, and provide the first neuroanatomical basis for lactate response in panic disorder.
Key words: Alzet pumps; anxiety; dorsomedial hypothalamus; GABA; medial preoptic nucleus; organum vasculosum lamina terminalis; stress; subfornical organ; tetrodotoxin
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