Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning

Cheryl Conrad, Donald D. MacMillan, Sergey Tsekhanov, Ryan L. Wright, Sarah E. Baran, Rita A. Fuchs

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Glucocorticoid receptor activation within the basolateral amygdala (BLA) during fear conditioning may mediate enhancement in rats chronically exposed to stress levels of corticosterone. Male Sprague-Dawley rats received corticosterone (400μg/ml) in their drinking water (days 1-21), a manipulation that was previously shown to cause hippocampal CA3 dendritic retraction. Subsequently, rats were adapted to the fear conditioning chamber (day 22), then trained (day 23), and tested for conditioned fear to context and tone (day 25). Training consisted of two tone (20s) and footshock (500ms, 0.25mA) pairings. In Experiment 1, muscimol (4.4nmol/0.5μl/side), a GABAergic agonist, was microinfused to temporarily inactivate the BLA during training. Rats given chronic corticosterone showed enhanced freezing to context, but not tone, compared to vehicle-supplemented rats. Moreover, BLA inactivation impaired contextual and tone conditioning, regardless of corticosterone treatment. In Experiment 2, RU486 (0, 0.3, and 3.0ng/0.2μl/side) was infused on training day to antagonize glucocorticoid receptors in the BLA. Corticosterone treatment enhanced fear conditioning to context and tone when analyzed together, but not separately. Moreover, RU486 (3.0ng/side) selectively exacerbated freezing to context in chronic corticosterone-exposed rats only, but failed to alter tone conditioning. Serum corticosterone levels were negatively correlated with contextual, not tone, conditioning. Altogether, these suggest that chronic corticosterone influences fear conditioning differently than chronic stress as shown previously. Moreover, chronic exposure to corticosteroids alters BLA functioning in a non-linear fashion and that contextual conditioning is influenced more than tone conditioning by chronic corticosterone and BLA glucocorticoid receptor stimulation.

Original languageEnglish (US)
Pages (from-to)185-199
Number of pages15
JournalNeurobiology of Learning and Memory
Volume81
Issue number3
DOIs
StatePublished - May 1 2004

Keywords

  • Fear conditioning
  • Hippocampus
  • Learning
  • Spatial memory
  • Stress
  • Type II receptor

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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