Panic results in unique molecular and network changes in the amygdala that facilitate fear responses.

Recurrent panic attacks (PAs) are a common feature of panic disorder (PD) and post-traumatic stress disorder (PTSD). Several distinct brain regions are involved in the regulation of panic responses, such as perifornical hypothalamus (PeF), periaqueductal gray, amygdala and frontal cortex. We have previously shown that inhibition of GABA synthesis in the PeF produces panic-vulnerable rats. Here, we investigate the mechanisms by which a panic-vulnerable state could lead to persistent fear. We first show that optogenetic activation of glutamatergic terminals from the PeF to the basolateral amygdala (BLA) enhanced the acquisition, delayed the extinction and induced the persistence of fear responses 3 weeks later, confirming a functional PeF-amygdala pathway involved in fear learning. Similar to optogenetic activation of PeF, panic-prone rats also exhibited delayed extinction. Next, we demonstrate that panic-prone rats had altered inhibitory and enhanced excitatory synaptic transmission of the principal neurons, and reduced protein levels of metabotropic glutamate type 2 receptor (mGluR2) in the BLA. Application of an mGluR2-positive allosteric modulator (PAM) reduced glutamate neurotransmission in the BLA slices from panic-prone rats. Treating panic-prone rats with mGluR2 PAM blocked sodium lactate (NaLac)-induced panic responses and normalized fear extinction deficits. Finally, in a subset of patients with comorbid PD, treatment with mGluR2 PAM resulted in complete remission of panic symptoms. These data demonstrate that a panic-prone state leads to specific reduction in mGluR2 function within the amygdala network and facilitates fear, and mGluR2 PAMs could be a targeted treatment for panic symptoms in PD and PTSD patients.

Pulse oximetry signals local anesthetic-induced methemoglobinemia.

An otherwise healthy patient with a fractured mandible was scheduled to undergo an open reduction under general anesthesia. Just before transport to the operating room, bimaxillary arch bars were placed under local anesthesia with 4% prilocaine and 1:200,000 epinephrine. Although induction of anesthesia and nasoendotracheal intubation were uneventful, pulse oximetry values fell to 89% despite adequate ventilation and an inspired oxygen concentration of 50%. Inquiry by the anesthesiologist and arterial blood gas measurements revealed that methemoglobinemia had developed in response to the large amount 576 mg) of prilocaine administered. A total of 150 mg of methylene blue administered in two doses corrected the problem. The oral surgeon, having recently switched to prilocaine because of a manufacturer's recall of lidocaine, was unaware of the potential of prilocaine to cause this disorder.