THE CIRCUMVENTRICULAR ORGANS FORM A POTENTIAL NEURAL PATHWAY FOR LACTATE SENSITIVITY - IMPLICATIONS FOR PANIC DISORDER

Patients with panic disorder experience panic attacks after intravenou s sodium lactate infusions by an as yet unexplained mechanism. Lactate elicits a panic-like response in rats with chronic dysfunction of GAB A neurotransmission in the dorsomedial hypothalamus (DMH). The circumv entricular organs, organum vasculosum lamina terminalis (OVLT) and sub fornical organ (SFO), are potential sites that could detect increases in plasma lactate levels and activate the DMH. To test this, we obtain ed baseline heart rate (HR) and blood pressure (BP) responses to lacta te infusions in rats fit with femoral arterial and venous catheters. N ext, unilateral chronic injection cannulae connected to an Alzet infus ion pump filled with the GABA synthesis inhibitor L-allylglycine (L-AG ) were implanted into the DMH. Another chronic injection cannula was i mplanted 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 cerebrospi nal fluid (ACSF) or tetrodotoxin (TTX) into the CVO sites. Injecting T TX into the OVLT completely blocked the lactate-induced response, wher eas TTX injections into the SFO or MePOA did not. Also, direct injecti ons of lactate (100 or 500 nl) into the OVLT elicited robust anxiety-l ike responses in these rats. These results suggest that the OVLT may b e the primary site that detects lactate infusions, activating an anxie ty-like response in a compromised DMH, and provide the first neuroanat omical basis for lactate response in panic disorder.