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Improved age-related deficits in cognitive performance and affective-like behavior following acute, but not repeated, 8-OH-DPAT treatments in rats: regulation of hippocampal FADD.

Abstract
The aims of this study were (1) to behaviorally phenotype rats at different ages for both cognitive performance and affect, (2) to evaluate the possible beneficial effects of 8-OH-DPAT (a 5-HT1A receptor agonist) treatments on improving age-related behavioral deficits, and (3) to uncover putative key brain targets (e.g., Fas-associated protein with death domain [FADD] and related partners) that might contribute to the observed age-related behavioral changes. The principal results showed that acute, but not repeated, 8-OH-DPAT treatments improved age-related deficits in cognitive performance and affect while induced hypothermia. Moreover, multifunctional FADD protein decreased with age specifically in the hippocampus (as compared to the prefrontal cortex) and was further decreased following acute 8-OH-DPAT. The major conclusions indicate a parallelism between the beneficial effects observed following acute 8-OH-DPAT on improving the negative consequences of aging on cognition and affect, together with the acute induction of hypothermia and hippocampal FADD regulation. Because these effects were not observed following repeated treatment (i.e., observed tolerance to acute hypothermia), the results suggest 5-HT1A receptors desensitization and/or the activation of compensatory adaptive mechanisms.
AuthorsElena Hernández-Hernández, Antonio Miralles, Susana Esteban, M Julia García-Fuster
JournalNeurobiology of aging (Neurobiol Aging) Vol. 71 Pg. 115-126 (11 2018) ISSN: 1558-1497 [Electronic] United States
PMID30138765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Inc. All rights reserved.
Chemical References
  • Fadd protein, rat
  • Fas-Associated Death Domain Protein
  • Serotonin Receptor Agonists
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
Topics
  • 8-Hydroxy-2-(di-n-propylamino)tetralin (administration & dosage)
  • Affect (drug effects, physiology)
  • Animals
  • Behavior, Animal (drug effects)
  • Fas-Associated Death Domain Protein (metabolism)
  • Hippocampus (drug effects, metabolism)
  • Hypothermia (chemically induced)
  • Male
  • Maze Learning (drug effects)
  • Rats, Sprague-Dawley
  • Serotonin Receptor Agonists (administration & dosage)

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