Original Article

Neuropsychopharmacology (2002) 27, 133–142. doi:10.1016/S0893-133X(02)00286-5

Downregulation of BDNF mRNA in the Hippocampal Dentate Gyrus after Re-exposure to Cues Previously Associated with Footshock

Ann M Rasmusson MD1,2, Libin Shi MD2 and Ronald Duman Ph.D1,2,3

  1. 1VA National Center for PTSD, Clinical Neuroscience Division, West Haven, CT USA
  2. 2Department of Psychiatry, Yale University School of Medicine, New Haven, CT USA
  3. 3Department of Pharmacology, Yale University School of Medicine, New Haven, CT USA

Correspondence: Dr Ann M Rasmusson, M.D., Psychiatry Service/116A VA Connecticut Healthcare System, 950 Campbell Ave., West Haven, CT 06516, Tel.: (203) 932-5711 ext. 2483 or 2464; Fax: (203) 937-3886; Page: (203) 867-3132; E-mail: ann.rasmusson@yale.edu

Received 20 August 2001; Revised 17 December 2001; Accepted 8 January 2002

Previous Presentations: Presentation for the 13th Annual Meeting for The International Society for Traumatic Stress Studies, November 6-10, 1997; Society for Neuroscience Abstracts, 23, 1997.

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Abstract

This study examined the effects of footshock stress and re-exposure to cues previously associated with footshock on expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus of male rats. Exposure to twenty 0.5-s 0.4-mA footshocks co-terminating with 70 dB, 5-s long pure tones over 60 min decreased dentate gyrus BDNF mRNA by 21.5%. Baseline BDNF mRNA levels returned to normal by two days after footshock exposure. Re-exposure for 60 min to the chamber and tones previously paired with 0.4 mA footshock decreased BDNF mRNA by 12%. Re-exposure to the conditioning chamber and tones previously paired with 0.6 mA footshock over 60 min decreased BDNF mRNA by 20.8%. The data suggest that psychological, as well as unconditioned physical stress, can decrease hippocampal BDNF mRNA. Possible implications for stress-related and other neuropsychiatric disorders associated with deficits in hippocampal function and volume, such as depression, post-traumatic stress disorder, and Alzheimer's Disease, are discussed.

Keywords:

BDNF mRNA; Hippocampus; Dentate gyrus; Footshock stress; Psychological stress; Male rats

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