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Alterations in the hippocampal phosphorylated CREB expression in drug state-dependent learning.

Abstract
The present study investigated the possible alterations of hippocampal CREB phosphorylation in drug state-dependent memory retrieval. One-trial step-down passive avoidance task was used to assess memory retrieval in adult male NMRI mice. Pre-training administration of ethanol (1g/kg, i.p.) induced amnesia. Pre-test administration of ethanol (1g/kg, i.p) or nicotine (0.7 mg/kg, s.c.) reversed ethanol-induced amnesia, indicating ethanol- or ethanol-nicotine induced state-dependent learning (STD). Using Western blot analysis, it was found that the p-CREB/CREB ratio in the hippocampus increased in the mice that showed successful memory retrieval as compared with untrained mice. In contrast, pre-training administration of ethanol (1g/kg, i.p.) decreased the hippocampal p-CREB/CREB ratio in comparison with the control group. The hippocampal p-CREB/CREB ratio enhanced in ethanol- and ethanol-nicotine induced STD. Moreover, memory impairment induced by pre-training administration of WIN (1 mg/kg, i.p.) improved in the animals that received pre-test administration of WIN (1 mg/kg, i.p.), ethanol (0.5 g/kg, i.p.) or nicotine (0.7 mg/kg, s.c.), suggesting a cross STD between the drugs. The p-CREB/CREB ratio in the hippocampus decreased in the of WIN-induced amnesia and STD groups in comparison with the control group. In addition, cross state-dependent learning between WIN and ethanol or nicotine was associated with the increase of the hippocampal p-CREB/CREB ratio. It can be concluded that phosphorylation of CREB in the hippocampus is a critical event underlying the interaction of co-administration of drugs on memory retrieval in passive avoidance learning.
AuthorsSakineh Alijanpour, Ameneh Rezayof, Houri Sepehri, Ladan Delphi
JournalBehavioural brain research (Behav Brain Res) Vol. 292 Pg. 109-15 (Oct 01 2015) ISSN: 1872-7549 [Electronic] Netherlands
PMID26055203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • Benzoxazines
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Morpholines
  • Naphthalenes
  • Ethanol
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Nicotine
Topics
  • Amnesia (chemically induced, metabolism)
  • Animals
  • Avoidance Learning (drug effects, physiology)
  • Benzoxazines (pharmacology)
  • Conditioning, Operant (drug effects)
  • Cyclic AMP Response Element-Binding Protein (metabolism)
  • Ethanol (pharmacology)
  • Hippocampus (drug effects, metabolism)
  • Male
  • Memory (drug effects)
  • Memory Disorders (chemically induced, metabolism)
  • Mice
  • Mice, Inbred Strains
  • Morpholines (pharmacology)
  • Naphthalenes (pharmacology)
  • Nicotine (pharmacology)
  • Phosphorylation (drug effects)

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