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Effects of post-training hippocampal injections of midazolam on fear conditioning. Learn Mem 2005;12(6):573-8

Date

12/03/2005

Pubmed ID

16322359

Pubmed Central ID

PMC1356174

DOI

10.1101/lm.51305

Scopus ID

2-s2.0-28844448660 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Benzodiazepines have been useful tools for investigating mechanisms underlying learning and memory. The present set of experiments investigates the role of hippocampal GABA(A)/benzodiazepine receptors in memory consolidation using Pavlovian fear conditioning. Rats were prepared with cannulae aimed at the dorsal hippocampus and trained with a series of white noise-shock pairings. In the first experiment, animals received intrahippocampal infusion of midazolam or vehicle immediately or 3 h after training. Then, 24 h later, freezing to the training context and the white noise were measured independently. Results show infusion of midazolam immediately, but not 3 h, after training selectively attenuates contextual fear conditioning. In the second experiment, animals received intrahippocampal infusions of an antisense oligodeoxynucleotide (ODN) targeting the alpha5 subunit of the GABA(A) receptor or a missense control for several days prior to training and testing. Immediately after training, animals received an infusion of either midazolam or vehicle. Western blots conducted after testing showed a significant decrease in alpha5-containing GABA(A) receptor protein. This reduction did not alter the effectiveness of midazolam immediately after training at impairing context fear memory. Therefore, alpha5-containing GABA(A) receptors may not contribute to the effects of midazolam on context fear conditioning when given immediately post-training.

Author List

Gafford GM, Parsons RG, Helmstetter FJ

Author

Fred Helmstetter PhD Professor in the Psychology / Neuroscience department at University of Wisconsin - Milwaukee




MESH terms used to index this publication - Major topics in bold

Animals
Association Learning
Conditioning, Classical
Drug Administration Schedule
Fear
Freezing Reaction, Cataleptic
GABA Modulators
Hippocampus
Male
Microinjections
Midazolam
Rats
Rats, Long-Evans
Receptors, GABA-A
Time Factors