Anxiety disorders are the most common of all mental health illnesses. Panic disorder (PD), a DSM recognized anxiety disorder, has a lifetime prevalence of 3.5%. The delay of treatment of this illness is further complicated by comorbidity with alcohol abuse or depression. These patients are also at increased risk of suicide. Rats bilaterally implanted with guide cannulae into the basolateral nucleus of the amygdala and injected for a maximum of 6 days with a subthreshold dose of the GABAA antagonist bicuculline methiodide exhibit an increase in heart rate (> 50 beats per minute), blood pressure, respiratory rate, and anxiety- like behavior, measured using the social interaction test on day 4 to 6 of drug treatment. The response exhibited by these rats is reminiscent of the symptoms experienced by panic disorder patients. Further, the BLA nucleus has been identified to be involved in the defense reaction as well as in conditioned fear- both responses are relevant to the development of the panic response. The objective of this research is utilize the primed rat to study the mechanisms underlying the panic response. Specifically, this research is aimed to: 1) determine the whether the panic-provoking agents yohimbine and fenfluramine are able to provoke similar responses in the BLA- primed rat; 2) determine if drugs effective in treating human panic attacks attenuate the panic response in the primed rat; and, 3) determine if the primed rat exhibits conditioned place avoidance. The methods used to explore the first aim will involve quantitating any change in heart rate, blood pressure, or respiratory rate during and after intravenous infusion of the panic provoking agent. Infusion of the drugs will be randomized and behavior will be measured after the monitoring period using the social interaction test. In this test the experimental rat will be paired with an untreated weight-matched (within 10 grams) rat in a 91 square cm arena for five minutes. Each rat will have been habituated to the arena and the lighting conditions prior to testing. Test duration will be 5 minutes. For the second aim, a Pavlovian conditioning test called conditioned place avoidance will be used to determine whether repeated intra- amygdala injections of BMI are aversive and therefore possibly indicative of the development of avoidance of the floor associated with the stimulus. Animals will be conditioned using tactile cues- floors constructed from perforated stainless steel or from stainless steel rods. For the third aim, BLA-primed rats will be treated twice daily for seven days with a prototypical SSRI or TCA and then challenged with an intra- amygdala injection of BMW. Treatments will be administered intraperitoneally, both acutely and chronically. The animal will be assessed for changes in response to the intra- amygdala injection of BMI. These three points will be used to study the underlying mechanism of the panic response. This mechanism of provoking the panic response is potentially beneficial in further understanding the neurobiology of the panic response on both the behavioral and cellular level.
| Shekhar, Anantha; Sajdyk, Tammy J; Gehlert, Donald R et al. (2003) The amygdala, panic disorder, and cardiovascular responses. Ann N Y Acad Sci 985:308-25 |
| Thielen, Shelley K; Shekhar, Anantha (2002) Amygdala priming results in conditioned place avoidance. Pharmacol Biochem Behav 71:401-6 |
