Translational approach to studying panic disorder in rats: Hits and misses

• The role of dorsal periaqueductal gray matter (DPAG) in panic is reviewed.
• DPAG lesions block respiratory-type panic attacks evoked by intravenously-injected potassium cyanide (KCN).
• KCN-evoked panics are potentiated by hypercapnia and blocked by clinically-effective treatments with panicolytics.
• DPAG-evoked panics lack `stress hormone' responses and are facilitated in the late diestrus of female rats.
• DPAG-evoked panics are sensitive to panicolytics and enhanced in neonatally-isolated adult rats.

Luiz Carlos Schenberg, Fagna Giacomin Schimitel, Rubia de Souza Armini, Cristian Setubal Bernabé, Caroline Azevedo Rosa, Sérgio Tufik, Claudia Janaina Torres Müller, Jeyce Willig Quintino-dos-Santos. Translational Approach to Studying Panic Disorder in Rats: Hits and Misses. Neurosci. Biobehav. Rev. XX (X) XXX-XXX, 2014. Panic disorder (PD) patients are specifically sensitive to 5–7% carbon dioxide. Another startling feature of clinical panic is the counterintuitive lack of increments in ‘stress hormones’. PD is also more frequent in women and highly comorbid with childhood separation anxiety (CSA). On the other hand, increasing evidence suggests that panic is mediated at dorsal periaqueductal grey matter (DPAG). In line with prior studies showing that DPAG-evoked panic-like behaviours are attenuated by clinically-effective treatments with panicolytics, we show here that (i) the DPAG harbors a hypoxia-sensitive alarm system, which is activated by hypoxia and potentiated by hypercapnia, (ii) the DPAG suffocation alarm system is inhibited by clinically-effective treatments with panicolytics, (iii) DPAG stimulations do not increase stress hormones in the absence of physical exertion, (iv) DPAG-evoked panic-like behaviours are facilitated in neonatally-isolated adult rats, a model of CSA, and (v) DPAG-evoked responses are enhanced in the late diestrus of female rats. Data are consistent with the DPAG mediation of both respiratory and non-respiratory types of panic attacks.