The 5-hydroxytryptamine agonist fenfluramine increases fos-like immunoreactivity in the brain

doi:10.1016/0006-8993(92)91037-F

Brain Research

Volume 594, Issue 1, 23 October 1992, Pages 131-137

https://doi.org/10.1016/0006-8993(92)91037-F Get rights and content

Abstract

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 μm thick) in a coronal plane from the anterior olfactory bulb to the brainstem. Brain slices were then stored at −40°C pending the tissue localization of 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 fentluramine, 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.

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Since this protein remains in the cell nucleus for a short period of time, its detection has been extensively used to map neuronal bodies activated by specific stimuli [30,71,82]. This increase in Fos protein expression has been shown to occur as a result of neuronal activation by a wide range of stimuli, such as convulsing agents [26,61], electrical current [51,72,79], neurotransmitters [70,83], immobilization stress [44,46], pain [17,45], injection of hypertonic saline [22,76] and exposure to threatening stimuli of the elevated plus-maze or T-maze [78,80]. Naive male Wistar rats weighing 240–260 g were used.
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Short communicationThe 5-hydroxytryptamine agonist fenfluramine increases fos-like immunoreactivity in the brain

Abstract

Physiol. Behav.

Peptides

Neurosci. Biobehav. Rev.

Peptides

Brain Res.

Neurosci. Lett.

Eur. J. Pharmacol.

Brain Res.

Neurosci. Biobehav. Rev.

Brain Res.

Brain Res. Bull.

Electrophysiology of the central serotonin system: receptor subtypes and transducer mechanisms

Ann. N.Y. Acad. Sci.

Role for brain corticotropin-releasing factor in the weight-reducing effects of chronic fenfluramine treatment in rats

Endocrinology

Control of ACTH secretion by the central nucleus of the amygdala: implication of the serotonergic system and its relevance to the glucocorticoid delayed negative feedback mechanism

Neuroendocrinology

Serotoninergic modulation of the pattern of eating and the profile of hunger-satiety in humans

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Biog. Amines

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Fos-Jun and the primary genomic response in the nervous system

Short communication
The 5-hydroxytryptamine agonist fenfluramine increases fos-like immunoreactivity in the brain