Journal Article

5-HT1A Agonist Properties Contribute to a Robust Response to Vilazodone in the Novelty Suppressed Feeding Paradigm

Alvaro L. Garcia-Garcia, Míriam Navarro-Sobrino, Gila Pilosof, Pradeep Banerjee, Alex Dranovsky and E. David Leonardo

in International Journal of Neuropsychopharmacology

Published on behalf of Collegium Internationale Neuro-Psychopharmacologicum

Volume 19, issue 10 ISSN: 1461-1457
Published online June 2016 | e-ISSN: 1469-5111 | DOI: https://dx.doi.org/10.1093/ijnp/pyw057

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  • Clinical Pharmacology and Therapeutics
  • Neurology
  • Psychiatry
  • Neuroscience

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Background:

Differences in 5-HT1A receptor function have been implicated in vulnerability to depression and in response to treatment. Adding 5-HT1A 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-HT1A 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-HT1A agonist activity, body temperature was measured after acute administration of vilazodone or fluoxetine, as administration of 5-HT1A 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-HT1A-dependent manner, consistent with agonist effects at 5-HT1A 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).

Conclusion:

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.

Keywords: vilazodone; 5-HT1A; fluoxetine; novelty suppressed feeding

Journal Article.  4190 words.  Illustrated.

Subjects: Clinical Pharmacology and Therapeutics ; Neurology ; Psychiatry ; Neuroscience

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