Ambalika Sarkar1, Parul Chachra1, Vidita A Vaidya2. 1. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India. 2. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India. Electronic address: vvaidya@tifr.res.in.
Abstract
BACKGROUND: Postnatal treatment with the selective serotonin reuptake inhibitor fluoxetine, evokes anxiety and depressive behavior in rodent models in adulthood. We examined the role of serotonin 2A (5-HT2A), serotonin 2C (5-HT2C) and serotonin 1A (5-HT1A) receptors, implicated in the development of anxiety, in the behavioral consequences of postnatal fluoxetine (PNFlx). METHODS: Control and PNFlx rat pups received concomitant treatment with the 5-HT2A/C receptor antagonist, ketanserin, the 5-HT2A receptor antagonist, MDL100907, the 5-HT2C receptor antagonist, SB242084, or the 5-HT1A receptor antagonist, WAY-100635, and were tested for behavior in adulthood. The effect of postnatal treatment with the 5-HT2A/C receptor agonist, DOI, on anxiety behavior was examined in adulthood. RESULTS: Postnatal 5-HT2A/C receptor blockade prevented PNFlx-evoked anxiety, attenuated depressive behavior, and normalized specific gene expression changes in the prefrontal cortex. Postnatal, selective 5-HT2A receptor antagonist treatment blocked PNFlx-evoked anxiety and depressive behavior, whereas 5-HT2C receptor antagonist treatment prevented anxiety but not depressive behavior. Postnatal 5-HT2A/C receptor stimulation was sufficient to evoke anxiety in adulthood. Serotonin 1A receptor blockade did not alter PNFlx-evoked anxiety but resulted in anxiety in control animals, an effect attenuated by concomitant 5-HT2A/C receptor blockade. CONCLUSIONS: Postnatal fluoxetine-evoked anxiety and depressive behavior, as well as specific gene expression changes in the prefrontal cortex, were prevented by 5-HT2A/C receptor blockade. Adult anxiety was evoked by either 5-HT2A/C receptor stimulation or 5-HT1A receptor blockade of naive control pups. Our findings implicate serotonin 2 receptors in the development of perturbed emotionality following PNFlx and suggest that an altered balance of signaling through 5-HT1A and 5-HT2A/C receptors in early life influences anxiety behavior.
BACKGROUND: Postnatal treatment with the selective serotonin reuptake inhibitor fluoxetine, evokes anxiety and depressive behavior in rodent models in adulthood. We examined the role of serotonin 2A (5-HT2A), serotonin 2C (5-HT2C) and serotonin 1A (5-HT1A) receptors, implicated in the development of anxiety, in the behavioral consequences of postnatal fluoxetine (PNFlx). METHODS: Control and PNFlxrat pups received concomitant treatment with the 5-HT2A/C receptor antagonist, ketanserin, the 5-HT2A receptor antagonist, MDL100907, the 5-HT2C receptor antagonist, SB242084, or the 5-HT1A receptor antagonist, WAY-100635, and were tested for behavior in adulthood. The effect of postnatal treatment with the 5-HT2A/C receptor agonist, DOI, on anxiety behavior was examined in adulthood. RESULTS: Postnatal 5-HT2A/C receptor blockade prevented PNFlx-evoked anxiety, attenuated depressive behavior, and normalized specific gene expression changes in the prefrontal cortex. Postnatal, selective 5-HT2A receptor antagonist treatment blocked PNFlx-evoked anxiety and depressive behavior, whereas 5-HT2C receptor antagonist treatment prevented anxiety but not depressive behavior. Postnatal 5-HT2A/C receptor stimulation was sufficient to evoke anxiety in adulthood. Serotonin 1A receptor blockade did not alter PNFlx-evoked anxiety but resulted in anxiety in control animals, an effect attenuated by concomitant 5-HT2A/C receptor blockade. CONCLUSIONS: Postnatal fluoxetine-evoked anxiety and depressive behavior, as well as specific gene expression changes in the prefrontal cortex, were prevented by 5-HT2A/C receptor blockade. Adult anxiety was evoked by either 5-HT2A/C receptor stimulation or 5-HT1A receptor blockade of naive control pups. Our findings implicate serotonin 2 receptors in the development of perturbed emotionality following PNFlx and suggest that an altered balance of signaling through 5-HT1A and 5-HT2A/C receptors in early life influences anxiety behavior.
Authors: Edênia C Menezes; Relish Shah; Lindsay Laughlin; K Yaragudri Vinod; John F Smiley; Catarina Cunha; Andrea Balla; Henry Sershen; Francisco X Castellanos; André Corvelo; Cátia M Teixeira Journal: J Neurosci Date: 2021-02-03 Impact factor: 6.167
Authors: Marco Bocchio; Giulia Fucsina; Lydia Oikonomidis; Stephen B McHugh; David M Bannerman; Trevor Sharp; Marco Capogna Journal: Neuropsychopharmacology Date: 2015-06-08 Impact factor: 7.853