P-CHLOROPHENYLALANINE AND FLUOXETINE INHIBIT D-FENFLURAMINE-INDUCED FOS EXPRESSION IN THE PARAVENTRICULAR NUCLEUS, CINGULATE CORTEX AND FRONTAL-CORTEX BUT NOT IN OTHER FOREBRAIN AND BRAIN-STEM REGIONS

`D-Fenfluramine, a putative serotonin releaser and reuptake inhibitor, is commonly prescribed for the treatment of obesity. Brain sites acti vated by D-fenfluramine have been mapped via the expression of the imm ediate early gene Fos. However, it is not clear that serotonin release in the brain mediates the effects of D-fenfluramine on Fos expression . The present study determined whether D-fenfluramine induces the expr ession of Fos in the brain through the release of serotonin. Rats were pretreated either with the serotonin depleting drug p-chlorophenylala nine (PCPA) or with the serotonin reuptake inhibitor fluoxetine. Both drugs inhibited D-fenfluramine-induced Fos expression in the cingulate cortex, frontal cortex, and the parvocellular subdivision of the para ventricular nucleus of the hypothalamus. Neither drug reduced D-fenflu ramine-induced Fos responses in several other brain areas, including t he caudate-putamen, amygdala, and brainstem regions such as the latera l parabrachial nucleus and nucleus of the solitary tract. These result s indicate regional specificity of mechanisms mediating D-fenfluramine -induced Fos expression. It is likely that D-fenfluramine-induced Fos expression at various sites in the brain is mediated via a combination of serotonin release and other, as yet unidentified, neurotransmitter s. (C) 1997 Elsevier Science B.V.