title: Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning.
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 (400 microg/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 (500 ms, 0.25 mA) pairings. In Experiment 1, muscimol (4.4 nmol/0.5 microl/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 3.0 ng/0.2 microl/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 (3.0 ng/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.
authors.affiliation: Department of Psychology, Arizona State University, Box 1104, Tempe, AZ 85287-1104, USA. conradc@asu.edu
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Conrad
authors.forename: Donald D
authors.initials: DD
authors.lastname: MacMillan
authors.forename: Sergey
authors.initials: S
authors.lastname: Tsekhanov
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Wright
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Baran
authors.forename: Rita A
authors.initials: RA
authors.lastname: Fuchs
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000008:administration & dosage / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000008:administration & dosage; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors*
chemical_list: D018755:GABA Agonists; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; C024357:corticosterone receptor; D009118:Muscimol; D015735:Mifepristone; D003345:Corticosterone