Inhibition of mRNA and protein synthesis in the CA1 region of the dorsal hippocampus blocks reinstallment of an extinguished conditioned fear response.
Memories are extinguished by the repeated presentation of a conditioned stimulus in the absence of an unconditioned stimulus to which it has been associated. It is believed that extinction establishes a new hierarchy of responses rather than an actual forgetting of the original response, which can usually reappear spontaneously after interruption of the extinction process. In this study, our aim was to analyze how profound extinction can be. Rats were trained in a one-trial, step-down inhibitory avoidance paradigm and then were exposed to several extinction sessions in which they were allowed to freely explore the apparatus for 30 sec after having stepped down. Extinction was complete enough so that there was no spontaneous recovery, and test session performance could not be enhanced by pharmacological agents with well known facilitative actions on retrieval. After being submitted to a new training session, control animals reacquired the avoidance response; however, animals failed to do so after receiving bilateral intra-CA1 infusions of either the protein synthesis inhibitor anisomycin or the mRNA synthesis blocker 5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole 15 min before the retraining session. Our results indicate that extinction can be carried to a point at which reinstallment of the conditioned response requires, like the original learning, de novo gene expression and protein synthesis in the CA1 region of the dorsal hippocampus.
Cammarota
Martín
M
Memorial Center, Department of Biochemistry, Instituto de Ciências Biológicas e da Saúde, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil.
Bevilaqua
Lia R M
LR
Kerr
Daniel
D
Medina
Jorge H
JH
Izquierdo
Iván
I
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002404:Catheterization; D003214:Conditioning, Classical / Q000187:drug effects*; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000502:physiology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*
D020536:Enzyme Activators; D018721:Muscarinic Agonists; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D004004:Dichlororibofuranosylbenzimidazole; D000841:Anisomycin