Interaction of Stress and Anxiogenic Drugs on Behaviors of Rats and Antagonism with Indomethacin
Uniformed Services University Of The Health Sciences Bethesda United States
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Panic disorder is a debilitating psychiatric condition characterized by the occurrence of discrete episodes of intense anxiety. Psychological and biological explanations for panic disorder have been offered, but there is no consensus regarding its etiology. Panic disorder patients are especially sensitive to the anxiety-provoking effects of certain pharmacological agents -- biological challenge agents BCA. Psychological models propose that conditioning history or cognitions explain this sensitivity to BCAs. Biological models of panic disorder propose physiological dysregulations to explain sensitivity to BCAs. This doctoral research examined the thesis that the greater sensitivity to BCAs in panic disorder patients is a result of stress-induced blood-brain barrier disruption. Several studies have reported that stress increases the permeability of the blood-brain barrier 888. Stress-induced blood-brain barrier disruption offers a parsimonious explanation for enhanced sensitivity to challenge agents -- as more of the agent enters the brain, stronger reactions occur. Two experiments were conducted with 200 male Wistar rats. Experiment 1examined the effects of 30 minutes of immobilization stress on behavioral responses elevated plus maze and open field test to various dosages of two anxiogenic drugsyohimbine, isoproterenol. Animals exposed to the stressor showed enhanced behavioral responses to both drugs. Experiment 2 examined the effects of pretreatment with a drug indomethacin, that antagonizes stress-induced blood-brain barrier disruption, followed by the two anxiogenic drugs on the same behavioral responses in different animals. Pre-treatment with indomethacin antagonized the stress-enhanced behavioral effects. These findings suggest that biologically-based theories regarding the etiology of panic disorder might be explained by effects of stress to disrupt the blood-brain barrier.
- Stress Physiology