title: 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.
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Sakineh
authors.initials: S
authors.lastname: Alijanpour
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), P. O .Box 19395-5746, Tehran, Iran. Electronic address: rezayof@khayam.ut.ac.ir.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Rezayof
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Houri
authors.initials: H
authors.lastname: Sepehri
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Ladan
authors.initials: L
authors.lastname: Delphi
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D048588:Benzoxazines / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D048588:Benzoxazines; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009025:Morpholines; D009281:Naphthalenes; D000431:Ethanol; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009538:Nicotine
keywords: Drug state-dependent learning; Hippocampus; p-CREB/CREB ratio