title: Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus.
abstract: Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus--nitric oxide (NO) acts as a neurotransmitter in the rat dorsolateral periaqueductal gray (dlPAG), a midbrain structure that modulates fear and defensive behavior. Since defensive reactions can be alleviated by anxiolytic/anti-panic drugs, the present study tested the effect of clomipramine, a serotonin re-uptake inhibitor, on the activation of NO-producing neurons in the dlPAG of rats exposed to a live predator. Double staining was performed using Fos immunohistochemistry and NADPH-diaphorase as techniques to mark neural activation and to detect NO-producing neurons, respectively. Male Wistar rats received acute or chronic (21 days) injections of saline or clomipramine (10 or 20 mg/kg/day) and were exposed to a live cat. The animals exhibited a robust defensive reaction accompanied by an increase in the number of Fos- and double-stained neurons in the dlPAG, suggesting that cat exposure activates NO-producing neurons. Such effects were not significantly attenuated by clomipramine treatments. The intensity of fear reaction correlated with the intensity of neural staining in the dlPAG, regardless the drug treatment. Thus, the present results reinforce the hypothesis that NO may coordinate defensive responses in the dlPAG and indicate that this mechanism may not be modulated by a serotonin re-uptake inhibitor.
authors.affiliation: Department of Pharmacology, Ribeirão Preto School of Medicine, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto-SP 14049-900, Brazil.
authors.forename: Fabrício A
authors.initials: FA
authors.lastname: Moreira
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D002452:Cell Count; D002997:Clomipramine / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005239:Fear; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D016761:Oncogene Proteins v-fos; D009252:NADPH Dehydrogenase; D002997:Clomipramine