title: 5-HT 1A Agonist Properties Contribute to a Robust Response to Vilazodone in the Novelty Suppressed Feeding Paradigm.
abstract: BACKGROUND
  Differences in 5-HT 1A receptor function have been implicated in vulnerability to depression and in response to treatment. Adding 5-HT 1A partial agonists to selective serotonin reuptake inhibitors has been touted as a strategy to increase their efficacy. Here we use the novelty suppressed feeding paradigm to compare the effects of vilazodone, a high-potency selective serotonin reuptake inhibitor, with high affinity for 5-HT 1A receptors to the reference selective serotonin reuptake inhibitor fluoxetine across several mouse strains that differ in their response to selective serotonin reuptake inhibitors.
  
  
  METHODS
  To confirm 5-HT 1A agonist activity, body temperature was measured after acute administration of vilazodone or fluoxetine, as administration of 5-HT 1A agonists induces hypothermia. We next used 3 strains of mice to examine the effects of the drugs on latency in the novelty suppressed feeding, a paradigm generally sensitive to chronic but not acute effects of antidepressants.
  
  
  RESULTS
  Vilazodone induces robust hypothermia and blocks stress-induced hyperthermia in a 5-HT 1A -dependent manner, consistent with agonist effects at 5-HT 1A autoreceptors. In 129SvEv mice, vilazodone (10mg/kg/d) reduces the latency to eat in the novelty suppressed feeding test within 8 days, while no effect of fluoxetine (20mg/kg/d) was detected at that time. In contrast, both vilazodone and fluoxetine are effective at decreasing latency to eat in the novelty suppressed feeding paradigm in a strain with low autoreceptor levels. In mice with higher autoreceptor levels, no significant difference was detected between fluoxetine and vehicle ( P=. 8) or vilazodone and vehicle ( P =.06).
  
  
  CONCLUSIONS
  In mice, vilazodone may offer advantages in time of onset and efficacy over a reference selective serotonin reuptake inhibitor in the novelty suppressed feeding test.
authors.forename: Alvaro L
authors.initials: AL
authors.lastname: Garcia-Garcia
authors.forename: Míriam
authors.initials: M
authors.lastname: Navarro-Sobrino
authors.forename: Gila
authors.initials: G
authors.lastname: Pilosof
authors.forename: Pradeep
authors.initials: P
authors.lastname: Banerjee
authors.forename: Alex
authors.initials: A
authors.lastname: Dranovsky
authors.forename: E David
authors.initials: ED
authors.lastname: Leonardo
keywords:  5-HT 1A; fluoxetine; novelty suppressed feeding; vilazodone