title: Corticosterone protects against memory impairments and reduced hippocampal BDNF levels induced by a chronic low dose of ethanol in C57BL/6J mice.
abstract: Acute low doses of ethanol can produce reversible memory deficits, but it is unknown whether they persist upon chronic use. We investigated whether the chronic intake of a low dose of ethanol induces memory impairments in the ethanol-preferring C57BL/6J mouse strain. Because stress precipitates alcohol abuse and the stress hormone corticosterone contributes to memory processes, ethanol consumption and toxic effects, we also determined the impact of co-treatment with corticosterone on these effects. BDNF contributes to memory function and toxic effects of ethanol, therefore its levels were quantified in the hippocampus and frontal cortex. Ethanol (1% in drinking water) and corticosterone (250 μg/mL) were administered using the two-bottle choice test to monitor their appetitive properties. Spatial and non-spatial memory performance was assessed using the spontaneous alternation, object recognition and object location tests. The chronic exposure to a low dose of ethanol caused spatial and non-spatial memory deficits after withdrawal associated with a reduction in hippocampal BDNF levels, which were prevented by co-treatment with corticosterone (~21 mg/kg/day). The protective effect of corticosterone on memory was no longer observed at higher doses (~41 mg/kg/day), but persisted for hippocampal BDNF levels. C57BL/6J mice did not develop an appetence for 1% ethanol, but the addition of corticosterone increased voluntary consumption of and preference for the ethanol+corticosterone solutions. Although acute low doses of corticosterone (1 mg/kg) were found to rescue established memory impairments, this is the first report of a protective effect of chronic doses of corticosterone in the range of 20-32 mg/kg, and particularly against memory deficits induced by alcohol.
authors.affiliation: Immunology and Neurodegeneration Group, School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom; marie.pardon@nottingham.ac.uk.
authors.forename: Mohamed Elsaed
authors.initials: ME
authors.lastname: Ebada
authors.forename: Liaque M
authors.initials: LM
authors.lastname: Latif
authors.forename: David A
authors.initials: DA
authors.lastname: Kendall
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Pardon
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002755:Choice Behavior; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D000431:Ethanol; D003345:Corticosterone