Post traumatic stress disorder (PTSD) and the substrates of anxiety enhancement in the adult rat

Budgell, John T. (1996) Post traumatic stress disorder (PTSD) and the substrates of anxiety enhancement in the adult rat. Masters thesis, Memorial University of Newfoundland.

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Abstract

This study was designed to investigate the effects of the benzodiazepine receptor antagonist, Flumazenil, on an ecologically sound model of post traumatic stress disorder (PTSD) (Experiment 1). In addition, the study examined the role of N-methyl D-aspartate (NMDA) receptor physiology in the genesis of anxiety-like behavior (ALB) (Experiment 2). -- Experiment 1 was designed to evaluate the effects of cat exposure and treatment with Flumazenil on anxiety and startle amplitude of Long-Evans rats. Animals were exposed to a cat for 5 minutes and then tested in the elevated plus maze 1 week later. Animals were injected with Flumazenil or sterile vehicle 10 minutes before behavioral testing. The following day startle amplitude was measured in the acoustic startle chamber. Animals given Flumazenil exhibited more head dips than vehicle injected controls. Furthermore, animals that were exposed to a cat exhibited more head dips than animals which were not exposed. In the elevated plus maze animals that were cat exposed showed significantly more anxiety-like behavior than animals that were not exposed to a cat. Flumazenil was behaviorally neutral in the elevated plus maze and had no effects on ALB of cat exposed rats. Moreover, the exposed animals showed a slower rate of habituation to the startle stimulus than animals that were non-exposed. The startle amplitudes of animals that were cat exposed or given Flumazenil were greater than for animals given vehicle and not exposed in the first 7 blocks of startle trials. However, by the end of the eighth block, all groups had reached an equivalent startle amplitude end point. -- Experiment 2 was designed to evaluate the neuropharmacology of stress induced increases in anxiety. Specifically, the role of NMDA receptors in the pathophysiology of anxiety were investigated. Animals were cannulated in the basolateral amygdala in the left or right hemisphere or bilaterally. In other animals cannulas were implanted, and they were then handled but not exposed to a cat or intracranial injection. Experimental animals were injected with either the NMDA receptor antagonist, MK-801, or sterile saline, as appropriate, 30 minutes prior to exposure to the cat. It was found that the operated controls spent significantly more time in the open arms of the plus maze than either vehicle or MK-801 groups, which did not differ from each other. Thus, cat exposure increased plus maze anxiety(decreased open arm exploration) one week after the exposure equally in both the vehicle and MK-801 groups. However, MK-801 partially blocked the effects of cat exposure on Risk Assessment when injected into the left amygdala or bilaterally. Finally, MK-801 into the right and left hemispheres reduced the magnitude of the startle amplitude to the level of an operated-handled non-exposed control. The implications for anxiety research and PTSD are discussed.

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