Glucocorticoid receptor antagonism in the basolateral amygdala and ventral hippocampus interferes with long-term memory of contextual fear.
The binding of glucocorticoids to the type II or glucocorticoid receptor (GR) is known to play a role in memory consolidation and long-term memory. The present series of studies investigated the locus for GR effects on learning and memory of contextual fear conditioning. The GR antagonist RU 38486 was administered peripherally (10, 20, or 30 mg/kg/ml), as well as centrally into the lateral ventricle (75 or 150 ng/2 microL), basolateral amygdala (BLA; 0.3, 3, or 30 ng/0.2 microL), dorsal hippocampus (DH; 30 ng/microL) or ventral hippocampus (VH; 30 ng/microL) prior to contextual fear conditioning. Peripheral administration of RU 38486 did not affect fear-related levels of freezing immediately following a footshock or in a long-term memory test 24 h later. However, administration into the lateral ventricle, BLA, or VH decreased freezing in a 24 h retention test, while leaving post-shock levels of freezing intact. Both post-shock and retention levels of freezing were unaffected in rats that received RU 38486 in the DH compared to vehicle controls; however, vehicle rats also displayed low levels of freezing during retention. The data indicate that GR activation within the BLA and VH is important for the establishment of long-term memory for contextual fear conditioning.
Donley
Melanie P
MP
Department of Psychology, Behavioral Neuroscience Program, University of Delaware, 108 Wolf Hall, Newark, DE 19716, USA.
Schulkin
Jay
J
Rosen
Jeffrey B
JB
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004777:Environment; D005239:Fear / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006727:Hormone Antagonists / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D015735:Mifepristone / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000502:physiology
D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone