Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT1A receptors

Using in vivo intracerebral microdialysis in conscious, freely moving rats, we examined the effect of flibanserin, a potential antidepressant drug with high affinity for human 5-HT1A receptors and four–50-fold lower affinity for 5-HT2A and D4 receptors, on basal extracellular concentrations of serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA) and noradrenaline (NA) in selected regions of the rat brain. Flibanserin at 3 and 10 mg kg−1 significantly reduced extracellular 5-HT in the prefrontal cortex (by 30 and 45%) and dorsal raphe (35 and 44%), but had no effect on extracellular 5-HT in the ventral hippocampus. The 3 and 10 mg kg−1 doses raised extracellular NA to a similar extent in the prefrontal cortex (47 and 50%). In all, 10 mg kg−1 raised extracellular DA in the prefrontal cortex (63%) whereas 3 mg kg−1 had no significant effect. Pretreatment with the selective 5-HT1A receptor antagonist WAY100,635 (0.3 mg kg−1) 30 min before 10 mg kg−1 flibanserin completely antagonized the latter's effects on extracellular 5-HT, DA and NA in the prefrontal cortex. WAY100,635 by itself had no effect on cortical extracellular monoamines. The results show that the stimulation of 5-HT1A receptors plays a major role in the effect of flibanserin on brain extracellular 5-HT, DA and NA. British Journal of Pharmacology (2003) 139, 1281–1288. doi:10.1038/sj.bjp.0705341