Effects of treatment with imipramine and clonazepam on an animal model of panic disorder.
Tonic GABAergic inhibition in the dorsomedial hypothalamus (DMH) has been shown to regulate a constellation of behavioral and physiological responses that resemble a human panic attack. The present study was aimed at testing if the panic-like response elicited by injecting gamma-aminobutyric acid (GABA) antagonists into the DMH can be blocked by pretreating the animals with the antipanic drugs, imipramine and clonazepam. Rats were fitted with arterial catheters and bilateral chronic microinjection cannulae in the DMH. Their baseline heart rate, respiratory rate, blood pressure and "anxiety" (measured by the social interaction test) responses to injection of the GABAA antagonist bicuculline methiodide (BMI) into the DMH were recorded. After treatment in a double-blind manner with vehicle, imipramine (5 and 15 mg/kg, 7 days), and clonazepam (5 mg/kg, 3 days), the response to BMI microinjection into the DMH was once again recorded. Both imipramine and clonazepam, but not vehicle treatments blocked the BMI response.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202.
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Shekhar
D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D002998:Clonazepam / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004311:Double-Blind Method; D007033:Hypothalamus, Middle / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D016584:Panic Disorder / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects
D018079:Receptors, GABA; C017069:bicuculline methiodide; D002998:Clonazepam; D007099:Imipramine; D001640:Bicuculline