Effects of contextual fear conditioning and pentylenetetrazol on panic-like reactions induced by dorsal periaqueductal gray stimulation with N-methyl-D-aspartate.

Abstract

Electrical or chemical stimulation of the dorsal periaqueductal gray (DPAG) has been accepted as an animal model of panic attacks. This study investigates the influence of anticipatory anxiety in the occurrence of panic-like behavior induced by N-methyl-D-aspartate (NMDA) microinjection into the DPAG of rats. Behavioral (i.e., contextual fear conditioning) and pharmacological (i.e., pentylenetetrazol) manipulations were employed as animal models of anticipatory anxiety. In the first experiment, animals exposed to contextual cues that had been previously associated with electric footshocks through contextual fear conditioning were less likely than non-conditioned control animals to display defensive reactions such as running and jumping in response to microinjection of NMDA (0.3 µl of 15.0 µg/µl) into the DPAG. In the second experiment, rats were injected intraperitoneally with the anxiogenic drug pentylenetetrazol (PTZ, 15 mg/kg) 5 minutes before receiving intra-DPAG microinfusion with the same dose of NMDA as in Experiment 1. Panic-related behaviors were registered in an experimental arena immediately after NMDA microinfusion. As compared with saline pre-treated animals, PTZ significantly attenuated NMDA-induced panic-like reactions. These results further demonstrate the usefulness of DPAG chemical stimulation as an animal model of panic attacks and suggest that behavioral and pharmacological activation of the brain mechanisms underlying anticipatory anxiety might exert an antipanic-like effect.