Brain neuronal activation induced by flibanserin treatment in female rats

Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is developed for the treatment of hypoactive sexual desire disorder in women, and its efficacy has been evidenced in several clinical studies. Flibanserin prosexual effects have been also evidenced in preclinical animal models. However, the mechanism of action of flibanserin remains not fully understood.

The aim of the present study was to examine brain neuronal activation in female rats treated with flibanserin, using single immunocytochemical labeling of Fos protein, a marker of neuronal activation, and co-localization of Fos and catecholaminergic marker.

Six groups of female rats received either acute or chronic administrations of vehicle, flibanserin 15 mg/kg or flibanserin 45 mg/kg. The brains were collected and processed for immunocytochemical labeling.

Acute flibanserin increased levels of Fos immunoreactivity in the nucleus accumbens, arcuate hypothalamic nucleus, locus coeruleus, lateral paragigantocellular nucleus, and nucleus of the solitary tract. Chronic 22-day treatment with flibanserin increased Fos expression in the medial preoptic area and arcuate nucleus of the hypothalamus, ventral tegmental area, locus coeruleus, and lateral paragigantocellular nucleus. Both acute and chronic flibanserin increased the density of activated catecholaminergic neurons in the ventral tegmental area but not in the locus coeruleus.

Altogether, our results showed that flibanserin, at the dose known to enhance female sexual motivation, preferentially activated the brain regions belonging to the mesolimbic dopaminergic pathway and hypothalamic structures involved in the integration of sexual cues related to sexual motivation.