Contrasting Effects of Pretraining, Posttraining, and Pretesting Infusions of Corticotropin-Releasing Factor into the Lateral Amygdala: Attenuation of Fear Memory Formation but Facilitation of its Expression

• Published in: Biological psychiatry (1969) Vol. 73; no. 4; pp. 353 - 359
• Main Authors: Isogawa, Koichi, Bush, David E.A, LeDoux, Joseph E
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.02.2013; Elsevier
• Subjects: Acoustic Stimulation; Amygdala; Amygdala - drug effects; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Conditioning, Classical - drug effects; corticotropin-releasing factor; Corticotropin-Releasing Hormone - administration & dosage; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroshock; Fear - drug effects; fear conditioning; fear-related disorders; Freezing Reaction, Cataleptic - drug effects; learning; Male; Medical sciences; memory; Memory - drug effects; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; corticotropin-releasing factor; learning; fear conditioning; memory; Amygdala; fear-related disorders; Facilitation; Affect affectivity; Memory; Central nervous system; Corticotropin releasing factor; Basal ganglion; Emotion emotionality; Encephalon; Hypothalamic hormone; Learning; Fear; Acquisition process; Attenuation; Conditioning; Hormone releasing factor; Amygdaloid nucleus
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2012.08.021

Background The lateral nucleus of the amygdala (LA) is a crucial part of the neural circuitry underlying the formation and storage of memories established through fear conditioning. To investigate corticotropin-releasing factor (CRF) contributions to fear memory in LA, the present experiments tested the effects of intra-LA infusions on the formation and expression of memory after Pavlovian fear conditioning. Methods In experiment 1, CRF was infused bilaterally into LA of rats 1 hour before fear conditioning training. Two days later, rats were tested for conditioned stimulus (CS)-elicited freezing behavior in a distinct context. In experiment 2, rats were infused with CRF in LA immediately after auditory fear conditioning and then tested 2 days later. In experiment 3, rats were fear conditioned and then 2 days later infused with CRF in LA 1 hour before fear memory testing to assess effects on the expression of fear memory. Finally, we repeated the pretraining and pretesting experiments with the central nucleus of the amygdala infusions. Results Rats given either pretraining or posttraining CRF infusions in LA showed dose-dependent suppression of CS-elicited freezing in the fear memory test session. In contrast, rats given pretesting CRF showed facilitation of CS-elicited freezing. Corticotropin-releasing factor infusions into the central nucleus of the amygdala had no effect when given before—training or testing. Conclusions Corticotropin-releasing factor infusions into LA impair the consolidation of memory for fear conditioning but enhance the expression of pre-established fear memories. These findings may have important implications for understanding mechanisms underlying contributions of CRF to fear-related disorders.