title: Long-term administration of the antidepressant vilazodone modulates rat brain monoaminergic systems.
abstract: Vilazodone has high affinity for the human 5-hydroxytryptamine1A (h5-HT1A) receptor and for the serotonin transporter (5-HTT). A previous in vivo microdialysis experiment showed that a single administration of vilazodone, dose-dependently increases extracellular 5-HT but not norepinephrine (NE) or dopamine (DA) levels in rat medial prefrontal cortex and ventral hippocampus. The effects of vilazodone on monoaminergic systems were assessed using single-unit extracellular recordings and microiontophoresis in the rat brain. Following depletion of 5-HT with para-chlorophenylalanine methyl-ester hydrochloride (PCPA), vilazodone still suppressed neuronal firing of dorsal raphe nucleus (DRN) 5-HT neurons to a similar extent than controls, indicating that this inhibition is via 5-HT1A receptors activation. Following 2-day intraperitoneal administration of vilazodone (5 mg/kg/day), there was a significant decrease in 5-HT neuronal firing which recovered to baseline levels by day 14 of administration, likely due to 5-HT1A autoreceptor desensitization. Two- and 14-day administration of vilazodone decreased the mean firing and bursting activities of ventral tegmental area (VTA) DA neurons, while only its repeated administration significantly dampened the mean firing rate of locus coeruleus (LC) NE neurons. Vilazodone acted as an agonist at 5-HT1A receptors, while showing a 5-HTT blocking capacity when injected acutely. After repeated vilazodone regimen, while there was no change in sensitivity of 5-HT1A receptors, the enhancement in 5-HT transmission yielded an increase in the tonic activation of these receptors located in the hippocampus.
authors.affiliation: University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Electronic address: mostafa.elmansari@theroyal.ca.
authors.forename: Mostafa
authors.initials: M
authors.lastname: El Mansari
authors.affiliation: University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Electronic address: agnes.crnic@gmail.com.
authors.forename: Agnes
authors.initials: A
authors.lastname: Crnic
authors.affiliation: University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Electronic address: chris.oosterhof@theroyal.ca.
authors.forename: Chris
authors.initials: C
authors.lastname: Oosterhof
authors.affiliation: University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Electronic address: pierre.blier@theroyal.ca.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors; D000069503:Vilazodone Hydrochloride / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D004298:Dopamine; D009638:Norepinephrine; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069503:Vilazodone Hydrochloride
keywords: Electrophysiology; Hippocampus; Major depressive disorder; Monoamines; Vilazodone