Fluoxetine attenuates the effects of pentylenetetrazol on rat freezing behavior and c-Fos expression in the dorsomedial periaqueductal gray

The aim of the study was to investigate the role of the periaqueductal gray (PAG) in anxiolytic-like actions of fluoxetine in animals treated with an anxiogenic drug, pentylenetetrazol (PTZ), and subjected to fear conditioning procedure. The data showed that PTZ given at the dose of 30 mg/kg 15 min before a retention trial significantly decreased freezing reaction (p < 0.01), and potently enhanced rat locomotor activity (p < 0.01), in comparison to the control group. These effects were reversed by prior (60 min) administration of fluoxetine (20 mg/kg). Simultaneously, PTZ significantly increased c-Fos expression in the dorsomedial periaqueductal gray (DMPAG), examined 2 h after the retention trial, in comparison to the control group (p < 0.01). Fluoxetine (20 mg/kg) administered 60 min before PTZ reversed this effect. PTZ given at the same dose and time interval in the open field test did not affect rat locomotor behavior. Importantly, fluoxetine pretreatment did not change PTZ concentration in brain tissue. Our experiment based on PTZ-enhanced aversive conditioning revealed that acutely administered fluoxetine antagonized PTZ-induced panic-like behavior, and this phenomenon was accompanied by inhibition of activity of DMPAG.