MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Fluoxetine Exposure during Adolescence Alters Responses to Aversive Stimuli in Adulthood

Author(s)
Iniguez, Sergio D.; Alcantara, Lyonna F.; Warren, Brandon L.; Riggs, Lace M.; Parise, Eric M.; Vialou, Vincent; Wright, Katherine N.; Dayrit, Genesis; Nieto, Steven J.; Wilkinson, Matthew B.; Lobo, Mary Kay; Neve, Rachael L.; Nestler, Eric J.; Bolaños-Guzmán, Carlos A.; ... Show more Show less
Thumbnail
DownloadIniguez-2014-Fluoxetine Exposure.pdf (2.715Mb)
PUBLISHER_POLICY

Publisher Policy

Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.

Terms of use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Metadata
Show full item record
Abstract
The mechanisms underlying the enduring neurobiological consequences of antidepressant exposure during adolescence are poorly understood. Here, we assessed the long-term effects of exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, during adolescence on behavioral reactivity to emotion-eliciting stimuli. We administered FLX (10 mg/kg, bi-daily, for 15 d) to male adolescent [postnatal day 35 (P35) to P49] C57BL/6 mice. Three weeks after treatment (P70), reactivity to aversive stimuli (i.e., social defeat stress, forced swimming, and elevated plus maze) was assessed. We also examined the effects of FLX on the expression of extracellular signal-regulated kinase (ERK) 1/2-related signaling within the ventral tegmental area (VTA) of adolescent mice and Sprague Dawley rats. Adolescent FLX exposure suppressed depression-like behavior, as measured by the social interaction and forced swim tests, while enhancing anxiety-like responses in the elevated plus maze in adulthood. This complex behavioral profile was accompanied by decreases in ERK2 mRNA and protein phosphorylation within the VTA, while stress alone resulted in opposite neurobiological effects. Pharmacological (U0126) inhibition, as well as virus-mediated downregulation of ERK within the VTA mimicked the antidepressant-like profile observed after juvenile FLX treatment. Conversely, overexpression of ERK2 induced a depressive-like response, regardless of FLX pre-exposure. These findings demonstrate that exposure to FLX during adolescence modulates responsiveness to emotion-eliciting stimuli in adulthood, at least partially, via long-lasting adaptations in ERK-related signaling within the VTA. Our results further delineate the role ERK plays in regulating mood-related behaviors across the lifespan.
Date issued
2014-01
URI
http://hdl.handle.net/1721.1/88542
Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Iniguez, S. D., L. F. Alcantara, B. L. Warren, L. M. Riggs, E. M. Parise, V. Vialou, K. N. Wright, et al. “Fluoxetine Exposure During Adolescence Alters Responses to Aversive Stimuli in Adulthood.” Journal of Neuroscience 34, no. 3 (January 15, 2014): 1007–1021.
Version: Final published version
ISSN
0270-6474
1529-2401

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.