title: Effects of post-training hippocampal injections of midazolam on fear conditioning.
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.
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Wisconsin 53201, USA.
authors.forename: Georgette M
authors.initials: GM
authors.lastname: Gafford
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Parsons
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Helmstetter
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D018757:GABA Modulators / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008845:Microinjections; D008874:Midazolam / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000378:metabolism; D013997:Time Factors
chemical_list: D018757:GABA Modulators; D011963:Receptors, GABA-A; D008874:Midazolam