The 5-hydroxytryptamine agonist fenfluramine increases Fos-like immunoreactivity in the brain.
This study was designed to assess the effects of the 5-hydroxytryptamine (5-HT) indirect agonist fenfluramine on the brain distribution of Fos- and corticotropin-releasing factor-like immunoreactivity (F-LI and CRF-LI). A single intraperitoneal injection of either DL-fenfluramine (25 mg/kg) or saline was given to resting Sprague-Dawley rats housed on a 12-12 h light-dark cycle and fed libitum. Sixty min following injections, rats were killed and brains removed and sliced (40 microns thick) in a coronal plane from the anterior olfactory bulb to the brainstem. Brain slices were then stored at -40 degrees C pending the tissue localization of F-LI and CRF-LI. F-LI and CRF-LI were determined by means of a double immunostaining procedure using the peroxidase-avidin:biotin complex (ABC) method. Fenfluramine injection led to a marked increase in F-LI in the caudate-putamen (CPu), the parvocellular division of the hypothalamic paraventricular nucleus (PVN), and the central amygdaloid nucleus (CeA). In the PVN, most of the F-LI was co-localized with CRF-LI. There was no attempt to identify which types of neurons displayed F-LI in CPu and CeA. While F-LI was readily observable in all rats treated with fenfluramine, it was not discernible in the control animals. This study provides evidence for an involvement of the immediate-early genes c-fos in the central action of fenfluramine.
Richard
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Département de Physiologie, Faculté de Médecine, Université Laval, Québec, Canada.
Rivest
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Rivier
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D000679:Amygdala / Q000737:chemistry / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000502:physiology; D002421:Caudate Nucleus / Q000737:chemistry / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000187:drug effects*; D011699:Putamen / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*
D016760:Proto-Oncogene Proteins c-fos; D011985:Receptors, Serotonin; D005277:Fenfluramine