The 5-HT1A and 5-HT2A/2C receptor antagonists WAY-100635 and ritanserin do not attenuate D-fenfluramine-induced fos expression in the brain.

ABSTRACT

D-Fenfluramine is a serotonin (5-hydroxytryptamine, 5-HT) releaser and reuptake inhibitor. It is used to study the neurochemical control of feeding and has been used to treat obesity. It has also been employed as a pharmacological tool to study changes in serotonergic function in psychiatric patients. Brain sites activated by D-fenfluramine via the release of 5-HT have been mapped via the expression of the immediate early gene c-fos. Studies in our laboratory have indicated that D-fenfluramine induces Fos in the hypothalamus and cortex through 5-HT release. The present study investigated whether 5-HT released by D-fenfluramine induces Fos expression in the brain by activating 5-HT1A or 5-HT2A/2C receptors. Rats were pretreated either with WAY-100635, a 5-HT1A antagonist, or ritanserin, a 5-HT2A/2C antagonist, prior to d-fenfluramine injection. Blockade of either 5-HT1A or 5-HT2A/2C receptors was not sufficient to suppress the Fos response to D-fenfluramine in any region of the brain examined, including the cingulate cortex, frontal cortex, caudate-putamen, paraventricular nucleus of the hypothalamus, amygdala, and brainstem. These results indicate that Fos response elicited by D-fenfluramine may be mediated by other receptors, in addition to the 5-HT1A or 5-HT2A/2C receptors.