TY - JOUR
T1 - Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate
T2 - Role of 5-HT 1A receptors
AU - Invernizzi, Roberto William
AU - Sacchetti, Giuseppina
AU - Parini, Stefania
AU - Acconcia, Sabrina
AU - Samanin, Rosario
PY - 2003/8
Y1 - 2003/8
N2 - 1. 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-HT 1A receptors and four-50-fold lower affinity for 5-HT 2A and D 4 receptors, on basal extracellular concentrations of serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA) and noradrenaline (NA) in selected regions of the rat brain. 2. 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. 3. Pretreatment with the selective 5-HT 1A 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. 4. The results show that the stimulation of 5-HT 1A receptors plays a major role in the effect of flibanserin on brain extracellular 5-HT, DA and NA.
AB - 1. 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-HT 1A receptors and four-50-fold lower affinity for 5-HT 2A and D 4 receptors, on basal extracellular concentrations of serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA) and noradrenaline (NA) in selected regions of the rat brain. 2. 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. 3. Pretreatment with the selective 5-HT 1A 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. 4. The results show that the stimulation of 5-HT 1A receptors plays a major role in the effect of flibanserin on brain extracellular 5-HT, DA and NA.
KW - 5-HT receptors
KW - 5-HT receptors
KW - 5-Hydroxytryptamine
KW - Antidepressant drugs
KW - Dopamine
KW - Dorsal raphe
KW - Microdialysis
KW - Noradrenaline
KW - Prefrontal cortex
KW - Ventral hippocampus
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U2 - 10.1038/sj.bjp.0705341
DO - 10.1038/sj.bjp.0705341
M3 - Article
C2 - 12890707
AN - SCOPUS:0041385717
VL - 139
SP - 1281
EP - 1288
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 7
ER -