Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood

Andrew M. Novick, Mackenzie Mears, Gina L Forster, Yanlin Lei, Shanaz M. Tejani-Butt, Michael J. Watt

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety-like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-d-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat. Quantitative autoradiography was used to measure 3H-MK-801 binding to NMDA receptors in regions of the medial prefrontal cortex, caudate putamen, nucleus accumbens, amygdala and hippocampus. Assessment of fear learning was achieved using an auditory fear conditioning paradigm, with freezing toward the auditory tone used as a measure of conditioned fear. Compared to controls, adolescent social defeat decreased adult NMDA receptor expression in the infralimbic region of the prefrontal cortex and central amygdala, while increasing expression in the CA3 region of the hippocampus. Previously defeated rats also displayed decreased conditioned freezing during the recall and first extinction periods, which may be related to the observed decreases and increases in NMDA receptors within the central amygdala and CA3, respectively. The alteration in NMDA receptors seen following adolescent social defeat suggests that dysfunction of glutamatergic systems, combined with mesocortical dopamine deficits, likely plays a role in the some of the long-term behavioral consequences of social stressors in adolescence seen in both preclinical and clinical studies.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalBehavioural Brain Research
Volume304
DOIs
StatePublished - May 1 2016
Externally publishedYes

Fingerprint

Fear
Learning
Dopamine
Prefrontal Cortex
Freezing
Hippocampus
Anxiety
Classical Conditioning
Dizocilpine Maleate
Caudate Nucleus
Putamen
Nucleus Accumbens
aspartic acid receptor
Amygdala
Autoradiography
Short-Term Memory
Cognition
Glutamic Acid

Keywords

  • Adolescence
  • Conditioned fear
  • NMDA
  • Social defeat
  • Stress

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood. / Novick, Andrew M.; Mears, Mackenzie; Forster, Gina L; Lei, Yanlin; Tejani-Butt, Shanaz M.; Watt, Michael J.

In: Behavioural Brain Research, Vol. 304, 01.05.2016, p. 51-59.

Research output: Contribution to journalArticle

Novick, Andrew M. ; Mears, Mackenzie ; Forster, Gina L ; Lei, Yanlin ; Tejani-Butt, Shanaz M. ; Watt, Michael J. / Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood. In: Behavioural Brain Research. 2016 ; Vol. 304. pp. 51-59.
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