Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model

Published on Dec 9, 2019in Scientific Reports3.998
· DOI :10.1038/S41598-019-55095-W
Annai J. Charlton1
Estimated H-index: 1
(University of Melbourne),
Carlos May3
Estimated H-index: 3
(University of Melbourne)
+ 4 AuthorsChristina J Perry15
Estimated H-index: 15
(University of Melbourne)
Chronic 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.
📖 Papers frequently viewed together
20142.74PLOS ONE
12 Citations
119 Citations
#1Ryan P. Vetreno (UNC: University of North Carolina at Chapel Hill)H-Index: 23
#2John Peyton Bohnsack (UIC: University of Illinois at Chicago)H-Index: 8
Last. Fulton T. Crews (UNC: University of North Carolina at Chapel Hill)H-Index: 86
view all 6 authors...
: Binge drinking and alcohol abuse are common during adolescence and cause lasting pathology. Preclinical rodent studies using the adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P]25 to P55) model of human adolescent binge drinking report decreased basal forebrain cholinergic (ie, ChAT+) neurons that persist into adulthood (ie, P56-P220). Recent studies link AIE-induced neuroimmune activation to cholinergic pathology, but the underlying molecular mec...
13 CitationsSource
#1Violette Coppens (University of Antwerp)H-Index: 9
#2Manuel Morrens (University of Antwerp)H-Index: 22
Last. Geert Dom (University of Antwerp)H-Index: 30
view all 4 authors...
Rationale Of late, evidence emerges that the pathophysiology of psychiatric diseases and their affiliated symptomatologies are at least partly contributable to inflammatory processes. Also in alcohol use disorders (AUD), this interaction is strongly apparent, with severely immunogenic liver cirrhosis being one of the most critical sequelae of chronic abusive drinking. This somatic immune system activation negatively impacts brain functioning and additionally, alcohol abuse appears to have a dire...
6 CitationsSource
#1Anna K. Radke (Miami University)H-Index: 13
#2Adrina Kocharian (NIH: National Institutes of Health)H-Index: 6
Last. Andrew Holmes (NIH: National Institutes of Health)H-Index: 88
view all 7 authors...
: There is a compelling evidence that midbrain dopamine (DA) neurons and their projections to the ventral striatum provide a mechanism for motivating reward-seeking behavior, and for utilizing information about unexpected reward prediction errors (RPEs) to guide behavior based on current, rather than historical, outcomes. When this mechanism is compromised in addictions, it may produce patterns of maladaptive behavior that remain obdurate in the face of contrary information and even adverse cons...
14 CitationsSource
#1Anna K. Radke (Miami University)H-Index: 13
#2Larry S. Zweifel (UW: University of Washington)H-Index: 34
Last. Andrew Holmes (NIH: National Institutes of Health)H-Index: 88
view all 3 authors...
Abstract The dopamine (DA) system is critical for various forms of learning about salient environmental stimuli. Prior work has shown that deletion of the obligatory NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor on neurons expressing the DA transporter (DAT) in mice results in reduced phasic release from DA-containing neurons. To further investigate the contribution of phasic DA release to reward-related learning and cognitive flexibility, the current study evaluated DAT-NR1 null mutan...
6 CitationsSource
#1Ellen R. Cullity (Florey Institute of Neuroscience and Mental Health)H-Index: 1
#2Heather B. Madsen (University of Melbourne)H-Index: 11
Last. Jee Hyun Kim (University of Melbourne)H-Index: 27
view all 4 authors...
: Healthy brain function requires a balance between the activity of dopamine receptor 1 (D1) and dopamine receptor 2 (D2). Alterations in this balance increase the risk for numerous developmental brain disorders. Indeed, D1 and D2 expression fluctuates throughout maturation, although there is conflicting evidence regarding the precise changes that occur. Here, we used stereology to investigate the developmental changes in the number of D1- or D2-expressing neurons in the prelimbic cortex, infral...
16 CitationsSource
#1Galaj E (SUNY: State University of New York System)H-Index: 1
#1E. Galaj (SUNY: State University of New York System)H-Index: 1
Last. Lisa M. Savage (SUNY: State University of New York System)H-Index: 28
view all 4 authors...
Abstract Adolescent binge drinking renders young drinkers vulnerable to alcohol use disorders in adulthood; therefore, understanding alcohol-induced brain damage and associated cognitive dysfunctions is of paramount importance. Here we investigated the effects of binge-like adolescent intermittent ethanol (AIE) exposure on nonspatial working memory, behavioral flexibility and cholinergic alterations in the nucleus accumbens (NAc) in male and female rats. On postnatal days P25–57 rats were intuba...
12 CitationsSource
#1David P Q Clark (Florey Institute of Neuroscience and Mental Health)H-Index: 1
#2Victoria M. Perreau (Florey Institute of Neuroscience and Mental Health)H-Index: 27
Last. Wah Chin Boon (Florey Institute of Neuroscience and Mental Health)H-Index: 27
view all 9 authors...
Traumatic brain injury triggers neuroinflammation that may contribute to progressive neurodegeneration. We investigated patterns of recruitment of astrocytes and microglia to inflammation after brain trauma by firstly characterising expression profiles over time of marker genes following TBI, and secondly by monitoring glial morphologies reflecting inflammatory responses in a rat model of traumatic brain injury (i.e. the lateral fluid percussion injury). Gene expression profiles revealed early e...
30 CitationsSource
#1Ariel M Zeleznikow-Johnston (Florey Institute of Neuroscience and Mental Health)H-Index: 4
#2Thibault Renoir (Florey Institute of Neuroscience and Mental Health)H-Index: 27
Last. Anthony J. Hannan (University of Melbourne)H-Index: 61
view all 6 authors...
Metabotropic glutamate receptor 5 (mGlu5) has been implicated in certain forms of synaptic plasticity and cognitive function. mGlu5 knockout (KO) mice and mGlu5 antagonists have been previously used to study the pathophysiology of schizophrenia as they have been shown respectively to display or induce endophenotypes relevant to schizophrenia. While schizophrenia presents with generalized cognitive impairments, the cognitive phenotype of mice lacking mGlu5 has so far only been explored using larg...
15 CitationsSource
#1Ryan P. Vetreno (UNC: University of North Carolina at Chapel Hill)H-Index: 23
#2Fulton T. Crews (UNC: University of North Carolina at Chapel Hill)H-Index: 86
Last. Fulton T. Crews (UNC: University of North Carolina at Chapel Hill)H-Index: 3
view all 2 authors...
Basal forebrain cholinergic neurons mature in adolescence coinciding with development of adult cognitive function. Preclinical studies using the rodent model of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-days on/2-days off from postnatal day [P]25 to P55) reveal persistent increases of brain neuroimmune genes that are associated with cognitive dysfunction. Adolescent intermittent ethanol exposure also reduces basal forebrain expression of choline acetyltransferase (ChAT), an enzyme ...
20 CitationsSource
#1Rebecca K. West (UH: University of Houston)H-Index: 2
#2Mark E. Maynard (UH: University of Houston)H-Index: 6
Last. J. Leigh Leasure (UH: University of Houston)H-Index: 17
view all 3 authors...
Abstract Excessive alcohol intake is associated with a multitude of health risks, especially for women. Recent studies in animal models indicate that the female brain is more negatively affected by alcohol, compared to the male brain. Among other regions, excessive alcohol consumption damages the frontal cortex, an area important for many functions and decision making of daily life. The objective of the present study was to determine whether the medial prefrontal cortex (mPFC) in female rats is ...
21 CitationsSource
Cited By10
#1Mojtaba Bagherzadeh (Sharif University of Technology)H-Index: 42
#2Arshad Bayrami (Sharif University of Technology)H-Index: 4
Last. Mojtaba Amini (University of Tabriz)H-Index: 25
view all 0 authors...
Abstract null null The current article discusses some unprecedented information about the improvement in forward osmosis (FO) performance of polyethersulfone/polyamide (PES/PA) membranes, mainly focused on water flux and selectivity along with resistance to fouling phenomenon; which itself is brought in by the introduction of pre-modified zeolitic imidazolate framework-8 MOF nanoparticles. An investigation has been conducted on ZIF-8 nanoparticles surface with hydrophilicity feature to evaluate ...
#1Nwabunwanne Nwokolo (University of Fort Hare)H-Index: 3
#2Matthew Chekwube Enebe (NWU: North-West University)H-Index: 3
Last. Oyeyemi Adigun Dada (UI: University of Ibadan)H-Index: 1
view all 5 authors...
Abstract The majority of plant infections caused by pathogens takes place beneath the soil surface. Soil borne pathogens' attack on food crops could result in shortage of food supply and increase in economic losses. Every soil harbors certain peculiar microbial communities comprising bacteria, fungi, archaea, viruses and others that could participate in plants’ defense. Plants and its holobiont interact to enhance plant tolerance to biotic stress. The basic lines of defense are the rhizosphere (...
#1Cihan Parlak (Abant Izzet Baysal University)H-Index: 7
Abstract null null Determination of detailed electronic and lattice dynamical properties of hexagonal SrGa2 binary system under external pressure with the aid of first-principles calculation methods is of great importance in terms of the basic characteristics of binary system. On this basis, the phonon dispersion curves are calculated by the high-symmetry directions and related phonon frequencies parameters at the Brillouin zone center using density functional perturbation theory when the elasti...
#1A.A. Othman (Assiut University)H-Index: 10
#2M.A. Osman (Assiut University)H-Index: 14
Last. E.M.M. Ibrahim (Sohag University)H-Index: 17
view all 4 authors...
Abstract Doped-ZnS nanoparticles (NPs) with various trivalent elements ions (Sb3+, In3+, and Bi3+) were synthesized using the sonochemical method. X-ray diffraction patterns proved the formation of the ZnS cubic phase without any phase separation with the doping process. The dependence of the crystallite size and the internal micro-strain on the dopant type was demonstrated. Optical absorption spectra of doped ZnS NPs revealed a decrease in the optical band gap due to the formation of extended d...
#1A.C. García-Wong (University of Lorraine)H-Index: 2
#2D. Pilloud (University of Lorraine)H-Index: 11
Last. Fabien Capon (University of Lorraine)H-Index: 10
view all 7 authors...
Abstract In this paper, vanadium nitride (VN) thin films have been deposited on Al substrates by reactive magnetron sputtering. Thermochromic VO2 films have been obtained by air oxidation of VN samples performed at three temperatures (450, 525 and 550 °C) at various durations (lower than 50 min). X-ray diffraction and Raman spectrometry of the VN oxidized films indicate that VO2 and V2O5 are the only phases produced during the oxidation process. Vanadium dioxide is the first oxide formed. It coe...
#1Jianlei Zhang (SHU: Shanghai University)H-Index: 2
#2Yueshan Jiang (SHU: Shanghai University)H-Index: 1
Last. Qijie Zhai (SHU: Shanghai University)H-Index: 29
view all 8 authors...
Abstract It was usually believed that the formation of intragranular κ-carbide in γ-austenite was attributed to spinodal decomposition followed by ordering reaction. In this work, near-atomic scale characterization of an austenite-based Fe-20Mn-9Al-3Cr-1.2C (wt. %) low-density steel, using (high-resolution) scanning transmission electron microscopy and atomic probe tomography, reveals that the initially-formed κ-carbides (2-3 nm in particle size) are featured with an ordered L′12 structure but w...
1 CitationsSource
Abstract null null This article contains a brief overview of plasmonic-based optical fiber analyte sensor's development over the last ten years. Since detection and monitoring of chemical, physical and biological parameters are highly reliant on optical fiber sensing technology due to numerous advantages. Here we outlined the cumulative introduction, past experimental research work on propagating surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR) module, then ends wit...
#1Furkan Kirik (Bezmialem Foundation University)H-Index: 1
#2Cansu Ekinci (Bezmialem Foundation University)H-Index: 2
Last. Hakan Ozdemir (Bezmialem Foundation University)H-Index: 8
view all 0 authors...
PURPOSE To compare intraretinal layers between the eyes in patients with myopic anisometropia, and evaluate the relationship between the layers with spherical equivalent (SE) and axial length (AL). METHODS In this retrospective study, the more myopic (MM) and fellow (F) eyes of 41 patients with myopic anisometropia, and 38 emmetropic (± 0.50 diopter) control (C) eyes were inclueded. Intraretinal layer segmentation was performed by optical coherence tomography. Global volumes of retinal layers an...
#1Sebnem GunesH-Index: 1
#2Zhonglei He (UCD: University College Dublin)H-Index: 6
Last. James F. CurtinH-Index: 31
view all 0 authors...
Platinum nanoparticles (PtNPs) have been investigated for their antioxidant abilities in a range of biological and other applications. The ability to reduce off-target CAP cytotoxicity would be useful in Plasma Medicine; however, little has been published to date about the ability of PtNPs to reduce or inhibit the effects of CAP. Here we investigate whether PtNPs can protect against CAP-induced cytotoxicity in cancerous and non-cancerous cell lines. PtNPs were shown to dramatically reduce intrac...
#1Rosa Paola Radice (University of Basilicata)H-Index: 2
#2Rocco Fiorentino (University of Basilicata)
Last. Giuseppe Martelli (University of Basilicata)H-Index: 12
view all 0 authors...
ABSTRACT null null H. pluvialis is a green unicellular microalgae and it is the first producer of natural astaxanthin in the world if subjected to stress conditions such as high light, high salinity and nutrient starvation. Astaxanthin is a powerful antioxidant used in many fields, such as aquaculture, pharmaceutical, food supplements and cosmetic. To obtain a large amount of astaxanthin, researcher focused on the optimisation of H. pluvialis growth. H. pluvialis has four different size growth s...