Increased fear learning, spatial learning as well as neophobia in Rgs2(-/-) mice

A. Raab*, S. Popp, K-P. Lesch, M. J. Lohse, M. Fischer, J. Deckert, L. Hommers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

Abstract

Anxiety disorders result from a complex interplay of genetic and environmental factors such as stress. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety. However, there is limited knowledge about the role of Rgs2 in fear learning and reactivity to stress. In this study, Rgs2(-/-) mice showed increased fear learning, male mice displayed increased contextual and cued fear learning, while females showed selectively enhanced cued fear learning. Male Rgs2(-/-) mice displayed increased long-term-contextual fear memory, but increased cued fear extinction. Learning in spatial non-aversive paradigms was also increased in Rgs2(-/-) mice. Female, but not male mice show increased spatial learning in the Barnes maze, while male mice showed enhanced place preference in the IntelliCage, rendering enhanced cognitive function non-specific for aversive stimuli. Consistent with the previous results, Rgs2 deletion resulted in increased innate anxiety, including neophobic behavior expressed as hypolocomotion, in three different tests based on the approach-avoidance conflict. Acute electric foot shock stress provoked hypolocomotion in several exploration-based tests, suggesting fear generalization in both genotypes. Rgs2 deletion was associated with reduced monoaminergic neurotransmitter levels in the hippocampus and prefrontal cortex and disturbed corresponding GPCR expression of the adrenergic, serotonergic, dopaminergic and neuropeptide Y system. Taken together, Rgs2 deletion promotes improved cognitive function as well as increased anxiety-like behavior, but has no effect on acute stress reactivity. These effects may be related to the observed disruption of the monoaminergic systems.
Original languageEnglish
Article numbere12420
Pages (from-to)1-14
Number of pages14
JournalGenes, Brain and Behavior
Volume17
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Anxiety
  • conditioning
  • cognition
  • fear
  • fear conditioning
  • GPCR
  • innate
  • learning
  • mice
  • mouse
  • neophobia
  • neurotransmitter
  • Rgs2
  • spatial
  • ANXIETY-LIKE BEHAVIOR
  • ELEVATED PLUS-MAZE
  • KNOCKOUT MICE
  • SYNAPTIC PLASTICITY
  • NEUROPEPTIDE-Y
  • PANIC DISORDER
  • WORKING-MEMORY
  • RGS2
  • RECEPTORS
  • MODEL

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