kim-chronicvoluntary-2019.pdf (3.54 MB)
Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model
journal contribution
posted on 2019-12-09, 00:00 authored by A J Charlton, C May, S J Luikinga, E L Burrows, J Hyun Kim, A J Lawrence, C J PerryChronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies.
History
Journal
Scientific ReportsVolume
9Issue
1Article number
18651Pagination
1 - 19Publisher
Springer Science and Business Media LLCLocation
Berlin, GermanyPublisher DOI
Link to full text
ISSN
2045-2322eISSN
2045-2322Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2019, The Author(s)Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC