Chronic Effects Of Alcohol Research Articles

Neuroimaging in alcohol use disorder: From mouse to man.

This article provides an overview of recent advances in understanding the effects of alcohol use disorders (AUD) on the brain from the perspective of magnetic resonance imaging (MRI) research in preclinical models and clinical studies. As a noninvasive investigational tool permitting assessment of morphological, metabolic, and hemodynamic changes over time, MRI offers insight into the dynamic course of alcoholism beginning with initial exposure through periods of binge drinking and escalation, sobriety, and relapse and has been useful in differential diagnosis of neurological diseases associated with AUD. Structural MRI has revealed acute and chronic effects of alcohol on both white and gray matter volumes. MR Spectroscopy, able to quantify brain metabolites in vivo, has shed light on biochemical alterations associated with alcoholism. Diffusion tensor imaging permits microstructural characterization of white matter fiber tracts. Functional MRI has allowed for elucidation of hemodynamicresponses at rest and during task engagement. Positron emission tomography, a non-MRI imaging tool, has led to a deeper understanding of alcohol-induced receptor and neurotransmitter changes during various stages of drinking and abstinence. Together, such in vivo imaging tools have expanded our understanding of the dynamic course of alcoholism including evidence for regional specificity of the effects of AUD, hints at mechanisms underlying the shift from casual to compulsive use of alcohol, and profound recovery with sustained abstinence.

Brain region specific glucagon-like peptide-1 receptors regulate alcohol-induced behaviors in rodents

Glucagon-like peptide 1 (GLP-1), an incretin hormone that reduces food intake, was recently established as a novel regulator of alcohol-mediated behaviors. Clinically available analogues pass freely into the brain, but the mechanisms underlying GLP-1-modulated alcohol reward remains largely unclear. GLP-1 receptors (GLP-1R) are expressed throughout the nuclei of importance for acute and chronic effects of alcohol, such as the laterodorsal tegmental area (LDTg), the ventral tegmental area (VTA) and the nucleus accumbens (NAc). We therefore evaluated the effects of bilateral infusion of the GLP-1R agonist exendin-4 (Ex4) into NAc shell, anterior (aVTA), posterior (pVTA) or LDTg on the acute alcohol-induced locomotor stimulation and memory of alcohol reward in the conditioned place preference (CPP) model in mice, as well as on alcohol intake in rats consuming high amounts of alcohol for 12 weeks. Ex4 into the NAc shell blocks alcohol-induced locomotor stimulation and memory of alcohol reward as well as decreases alcohol intake. The GLP-1R expression in NAc is elevated in high compared to low alcohol-consuming rats. On the contrary, GLP-1R activation in the aVTA does not modulate alcohol-induced behaviors. Ex4 into the pVTA prevents alcohol-induced locomotor simulation, but does neither modulate CPP-dependent alcohol memory nor alcohol intake. Intra-LDTg-Ex4 attenuates alcohol-induced locomotor stimulation and reduces alcohol intake, but does not affect memory of alcohol reward. Collectively, these data provide additional knowledge of the functional role of GLP-1R in reward-related areas for alcohol-mediated behaviors and further support GLP-1R as a potential treatment target for alcohol use disorder.

Tipsy neural stem cells: chronic effects of alcohol on the brain.

Tipsy neural stem cells: chronic effects of alcohol on the brain.

Qualitative Analysis of Alcohol’s Acute Effect on Vocal Range

Alcoholic beverages are the most popular human-produced drinks in history. Whether it is wine, beer, or hard liquor, alcoholic beverages are included in all aspects of society. Presidents, town drunks, and the greatest musical sensations are seen drinking alcoholic beverages both at work and at home. In terms of its effects on individuals, alcohol is deemed to be a poison to the body, and drinking too much can destroy your liver and your body as a whole. This puts public speakers, political leaders, and specifically singers in an odd position when it comes to balancing casual alcohol consumption and retaining their vocal health. Scientific study of this subject is necessary, as well as close consideration of the effects of alcohol on singer’s lives and careers. There is already extensive research pertaining to the chronic effects of alcohol on the body. In terms of acute alcohol ingestion, research does not exist to the same level of detail or quality. The effect of alcohol on vocal range, both chronic and acute, has not been studied thoroughly. Alcohol has many negative effects on the voice. In this study, we suggest that acute alcohol ingestion may decrease the vocal range of individuals.

Using Mismatch Negativity to Investigate the Pathophysiology of Substance Use Disorders and Comorbid Psychosis.

Substance use disorders (SUDs) have a devastating impact on society and place a heavy burden on health care systems. Given that alcohol, tobacco, and cannabis use have the highest prevalence, further understanding of the underlying pathophysiology of these SUDs is crucial. Electroencephalography is an inexpensive, temporally superior, and translatable technique which enables investigation of the pathobiology of SUDs through the evaluation of various event-related potential components, including mismatch negativity (MMN). The goals of this review were to investigate the effects of acute and chronic alcohol, tobacco, and cannabis use on MMN among nonpsychiatric populations and patients with comorbid psychosis. A literature search was performed using the database PubMed, and 36 articles met our inclusion and exclusion criteria. We found a pattern of attenuation of MMN amplitude among patients with alcoholism across acute and chronic alcohol use, and this dysregulation was not heritable. Reports were limited, and results were mixed on the effects of acute and chronic tobacco and cannabis use on MMN. Reports on comorbid SUDs and psychosis were even fewer, and also presented mixed findings. These preliminary results suggest that MMN deficits may be associated with SUDs, specifically alcohol use disorder, and serve as a possible biomarker for treating these common disorders.

Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice.

There is a clear need for discovery of effective medications to treat behavioral pathologies associated with alcohol addiction, such as chronic drinking. The goal of this preclinical study was to assess effects of chronic alcohol drinking on the nucleus accumbens (NAcb) proteome to identify and validate novel targets for medications development. Two-dimensional difference in-gel electrophoresis (2D-DIGE) with matrix-assisted laser desorption ionization tandem time-of-flight (MALDI-TOF/TOF) was used to assess effects of chronic voluntary home-cage (24-h access) alcohol drinking on the NAcb proteome of C57BL/6J mice. To extend these findings to a model of alcohol self-administration and reinforcement, we investigated potential regulation of the positive reinforcing effects of alcohol by the target protein glutathione S-transferase Pi 1 (GSTP1) using a pharmacological inhibition strategy in mice trained to self-administer alcohol or sucrose. Expression of 52 unique proteins in the NAcb was changed by chronic alcohol drinking relative to water control (23 upregulated, 29 downregulated). Ingenuity Pathway Analysis showed that alcohol drinking altered an array of protein networks associated with neurological and psychological disorders, molecular and cellular functions, and physiological systems and development. DAVID functional annotation analysis identified 9 proteins (SNCA, GSTP1, PRDX3, PPP3R1, EIF5A, PHB, PEBP1/RKIP, GAPDH, AND SOD1) that were significantly overrepresented in a functional cluster that included the Gene Ontology categories "response to alcohol" and "aging." Immunoblots confirmed changes in Pebp1 (RKIP) and GSTP1 in NAcb with no change in amygdala or frontal cortex, suggesting anatomical specificity. Systemic inhibition of GSTP1 with Ezatiostat (0-30mg/kg, i.p.) dose-dependently reduced the reinforcing effects of alcohol as measured by operant self-administration, in the absence of motor effects. Sucrose self-administration was also reduced but in a manner associated with nonspecific motor inhibition. Protein expression profiling identified an array of proteins and networks in the NAcb, including GSTP1, that are novel molecular targets of chronic alcohol drinking. Pharmacological inhibition of GSTP1 significantly reduced the positive reinforcing effects of alcohol, which regulate repetitive use and abuse liability. The observation that this protein was both upregulated after chronic drinking and that its inhibition could modulate the reinforcing properties of alcohol suggests that it is a key target for alcohol-related pathologies. Proteomic strategies combined with specific preclinical models has potential to identify and validate novel targets of alcohol that may be useful in the medical management of alcohol addiction.

Histone deacetylases mediate GABAA receptor expression, physiology, and behavioral maladaptations in rat models of alcohol dependence.

Alcohol use disorders are chronic debilitating diseases characterized by severe withdrawal symptoms that contribute to morbidity and relapse. GABAA receptor (GABAAR) adaptations have long been implicated in the chronic effects of alcohol and contribute to many withdrawal symptoms associated with alcohol dependence. In rodents, GABAAR hypofunction results from decreases in Gabra1 expression, although the underlying mechanism controlling Gabra1 expression after chronic ethanol exposure is still unknown. We found that chronic ethanol exposure using either ethanol gavage or two-bottle choice voluntary access paradigms decreased Gabra1 expression and increased Hdac2 and Hdac3 expression. Administration of the HDAC inhibitor trichostatin A (TSA) after chronic ethanol exposure prevents the decrease in Gabra1 expression and function as well as the increase in Hdac2 and Hdac3 expression in both the cortex and the medial prefrontal cortex (mPFC). Chronic ethanol exposure and withdrawal, but not acute ethanol exposure or acute withdrawal, cause a selective upregulation of HDAC2 and HDAC3 associated with the Gabra1 promoter that accompanies a decrease in H3 acetylation of the Gabra1 promoter and the reduction in GABAAR α1 subunit expression. TSA administration prevented each of these molecular events as well as behavioral manifestations of ethanol dependence, including tolerance to zolpidem-inducedloss of righting reflex, reduced open-arm time in the elevated plus maze, reduced center-time and locomotor activity in the open-field assay, and TSA reduced voluntary ethanol consumption. The results show how chronic ethanol exposure regulates the highly prominent GABAAR α1 subunit by an epigenetic mechanism that represents a potential treatment modality for alcohol dependence.

Binge Drinking and the Young Brain: A Mini Review of the Neurobiological Underpinnings of Alcohol-Induced Blackout.

Binge drinking has significant effects on memory, particularly with regards to the transfer of information to long-term storage. Partial or complete blocking of memory formation is known as blackout. Youth represents a critical period in brain development that is particularly vulnerable to alcohol misuse. Animal models show that the adolescent brain is more vulnerable to the acute and chronic effects of alcohol compared with the adult brain. This mini-review addresses the neurobiological underpinnings of binge drinking and associated memory loss (blackout) in the adolescent and young adult period. Although the extent to which there are pre-existing versus alcohol-induced neurobiological changes remains unclear, it is likely that repetitive binge drinking in youth has detrimental effects on cognitive and social functioning. Given its role in learning and memory, the hippocampus is a critical region with neuroimaging research showing notable changes in this structure associated with alcohol misuse in young people. There is a great need for earlier identification of biological markers associated with alcohol-related brain damage. As a means to assess in vivo neurochemistry, magnetic resonance spectroscopy (MRS) has emerged as a particularly promising technique since changes in neurometabolites often precede gross structural changes. Thus, the current paper addresses how MRS biomarkers of neurotransmission (glutamate, GABA) and oxidative stress (indexed by depleted glutathione) in the hippocampal region of young binge drinkers may underlie propensity for blackouts and other memory impairments. MRS biomarkers may have particular utility in determining the acute versus longer-term effects of binge drinking in young people.

Sexually dimorphic structural abnormalities in major connections of the medial forebrain bundle in alcoholism.

BackgroundThe mesocorticolimbic system is particularly susceptible to the effects of chronic alcoholism. Disruption of this system has been linked to drug seeking and the development of Reward Deficiency Syndrome, a neurobiological framework for describing the development and relapsing patterns of addictions. In this study, we evaluated the association of alcoholism and sex with major connections of the medial forebrain bundle (MFB), a prominent mesocorticolimbic fiber pathway connecting the ventral tegmental area with the basal forebrain. Given sex differences in clinical consequences of alcohol consumption, we hypothesized that alcoholic men and women would differ in structural abnormalities of the MFB.MethodsDiffusion magnetic resonance imaging (dMRI) data were acquired from 30 abstinent long-term alcoholic individuals (ALC; 9 men) and 25 non-alcoholic controls (NC; 8 men). Major connections of the MFB were extracted using multi-tensor tractography. We compared groups on MFB volume, fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD), with hemisphere and sex as independent variables. We also evaluated associations between abnormal structural measures and drinking measures.ResultsAnalyses revealed significant group-by-sex interactions for FA and RD: while ALC men had lower FA and higher RD compared to NC men, ALC women had higher FA and lower RD compared to NC women. We also detected a significant negative association between FA and number of daily drinks in ALC women.ConclusionAlcoholism is associated with sexually dimorphic structural abnormalities in the MFB. The results expand upon other findings of differences in brain reward circuitry of alcoholic men and women.

Chronic moderate alcohol drinking alters insulin release without affecting cognitive and emotion-like behaviors in rats.

Because the consumption of alcoholic beverages prevails in society, its effects on diabetes risk is a subject of interest. Extant literature on this issue often disagrees. Here, we probed the effects of chronic moderate ethanol consumption on glucose metabolism in rats. The effect of chronic moderate alcohol drinking on depression- and anxiety-like behaviors and memory was also explored. Adolescent male and female Long-Evans rats consumed saccharin-sweetened 5% (1 week) and 10% ethanol (7 weeks) under a 7.5-h/day (Monday-Friday) access schedule. This exposure was followed by sucrose preference and elevated plus maze (EPM) tests during an intervening week, before a 6-week intermittent-access (Monday, Wednesday, Friday) to 20% unsweetened ethanol in a 2-bottle choice drinking paradigm was implemented (EtOH). A free-feeding control group received water (Water). Our prior work revealed that voluntary ethanol consumption decreases food intake in rats. Hence, a second control group that received water was mildly food-restricted (FR), and their average body weight was matched to that of the EtOH group. During the week following week 6 of intermittent-access to 20% ethanol, rats were submitted to sucrose preference, EPM, and novel object recognition (NOR) tests. Insulin response to a glucose load was subsequently assessed via an oral glucose tolerance test (OGTT). Rats attained and maintained blood ethanol concentrations of ∼55mg/dL that correlated with the dose of sweetened 10% ethanol ingested. Relative to intake by Water controls, EtOH rats consumed less chow. There was no body weight difference between both groups. Neither sex of EtOH rats showed increased depression- and anxiety-like behaviors, as respectively measured by sucrose preference and EPM, nor did they show deficit in object recognition memory during abstinence. Male EtOH rats, however, showed signs of reduced general activity on the EPM. During OGTT, male EtOH rats showed a time-dependent potentiation of insulin release for proper glucose clearance. Such an effect was not observed in females. This landmark study shows that chronic moderate alcohol consumption can have negative metabolic consequences in the absence of overt behavioral deficits, especially in males.

Salivary immune proteins monitoring can help detection of binge and chronic alcohol drinkers: Preliminary findings

BackgroundWe compared effects of binge and chronic alcohol drinking on oral health and salivary immunity proteins. MethodsThe study involved males: 13 healthy social-drinking (C), 10 alcohol-dependent after chronic alcohol-intoxication (A), and 8 binge-drinkers after a single binge-drinking session (B). We compared periodontal/dental state and salivary immune proteins (lactoferrin –Lf, lysozyme –Lz, oral peroxidase –OPO, immunoglobulin A –IgA) in all groups. ResultsGroup A had worse dental and periodontal states than group C and B. Group B had a lower OPO activity and Lz concentration, and a higher IgA concentration in comparison to group C. Group A had a higher OPO activity than group C. Group B had a lower Lz and a higher LF and IgA outputs than C. Group A had a lower IgA output and a strong tendency of Lf and Lz outputs to be lower than in group C. Positive correlations were found between alcohol amounts and OPO and Lf output in group A, with no such correlations in group B. Only IgA concentration in group B and OPO activity in group A have potential to be markers that help to differentiate binge from chronic alcohol drinking, and OPO activity had better accuracy than IgA. ConclusionBinge alcohol consumption resulted in specific disturbances in salivary innate immunity (Lz), whereas chronic drinking led to disturbances in both adaptive and innate immunity (IgA, Lz and Lf). There is potential applicability of raised salivary IgA concentration and especially OPO activity in binge and chronic drinking detection and differential-diagnosis.

The burden of alcohol-related morbidity and mortality in Ottawa, Canada.

ObjectivesAlcohol-related morbidity and mortality are significant public health issues. The purpose of this study was to describe the prevalence and trends over time of alcohol consumption and alcohol-related morbidity and mortality; and public attitudes of alcohol use impacts on families and the community in Ottawa, Canada.MethodsPrevalence (2013–2014) and trends (2000–2001 to 2013–2014) of alcohol use were obtained from the Canadian Community Health Survey. Data on paramedic responses (2015), emergency department (ED) visits (2013–2015), hospitalizations (2013–2015) and deaths (2007–2011) were used to quantify the acute and chronic health effects of alcohol in Ottawa. Qualitative data were obtained from the “Have Your Say” alcohol survey, an online survey of public attitudes on alcohol conducted in 2016.ResultsIn 2013–2014, an estimated 595,300 (83%) Ottawa adults 19 years and older drank alcohol, 42% reported binge drinking in the past year. Heavy drinking increased from 15% in 2000–2001 to 20% in 2013–2014. In 2015, the Ottawa Paramedic Service responded to 2,060 calls directly attributable to alcohol. Between 2013 and 2015, there were an average of 6,100 ED visits and 1,270 hospitalizations per year due to alcohol. Annually, alcohol use results in at least 140 deaths in Ottawa. Men have higher rates of alcohol-attributable paramedic responses, ED visits, hospitalizations and deaths than women, and young adults have higher rates of alcohol-attributable paramedic responses. Qualitative data of public attitudes indicate that alcohol misuse has greater repercussions not only on those who drink, but also on the family and community.ConclusionsResults highlight the need for healthy public policy intended to encourage a culture of drinking in moderation in Ottawa to support lower risk alcohol use, particularly among men and young adults.

Changes of the intestinal microbiota during chronic alcohol intake

This paper examines the influence of chronic alcoholic intoxication on the qualitative and quantitative composition of the intestinal microbiota in patients with syndrome of alcohol dependence. The authors describe chronic alcoholic intoxication, accompanied by significant violations of homeostasis, which is manifested by changes in protein, carbohydrate, lipid, and mineral metabolism. The authors examine the role of alcohol as one of the main factors that affect dysbiotic shifts in the normal microbiota of human intestines. The paper presents the results of the comparison found earlier in the course of experimental work, significant changes of the intestinal microbiota of rats subjected to chronic alcoholism and clinical results of the study of the microbial landscape in patients with syndrome of alcohol dependence. The authors established that under the influence of alcohol there is a statistically significant reduction in saccharolytic microbiota. The obtained data are a part of a clinic-experimental study of changes in the state of resistance of the organism exposed to the chronic effects of alcohol and can serve as a basis for further study of the intestinal microbiota changes, which is an important component of a personalized approach to the definition of tactics of treatment and rehabilitation of people with the syndrome of alcohol dependence.

Examining the effects of alcohol on GABAA receptor mRNA expression and function in neural cultures generated from control and alcohol dependent donor induced pluripotent stem cells.

Factors influencing the development of alcohol-use disorder (AUD) are complex and heterogeneous. While animal models have been crucial to identifying actions of alcohol on neural cells, human-derived invitro systems that reflect an individual's genetic background hold promise in furthering our understanding of the molecular and functional effects of alcohol exposure and the pathophysiology of AUD. In this report, we utilized induced pluripotent stem cell (iPSCs)-derived neural cell cultures obtained from healthy individuals (CTLs) and those with alcohol dependence (ADs) to 1) examine the effect of 21-day alcohol exposure on mRNA expression of three genes encoding GABAA receptor subunits (GABRA1, GABRG2, and GABRD) using quantitative PCR, and 2) examine the effect of acute and chronic alcohol exposure on GABA-evoked currents using whole-cell patch-clamp electrophysiology. iPSCs from CTLs and ADs were differentiated into neural cultures enriched for forebrain-type excitatory glutamate neurons. Following 21-day alcohol exposure, significant treatment effects were observed in GABRA1, GABRG2, and GABRD mRNA expression. A modestly significant interaction between treatment and donor phenotype was observed for GABRD, which was increased in cell cultures derived from ADs. No effect of acute or chronic alcohol was observed on GABA-evoked currents in neurons from either CTLs or ADs. This work extends findings examining the effects of alcohol on the GABAA receptor in human cell invitro model systems.

Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals

IntroductionChronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys. MethodsAdolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use. Resultsdemonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas. DiscussionThe current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function.

Acute and chronic effects of alcohol on autonomic function during sleep

Acute and chronic effects of alcohol on autonomic function during sleep

Effect of chronic alcoholism on neuronal nuclear size and neuronal population in the mammillary body and the anterior thalamic complex of man

The effect of chronic alcoholism on neuronal nuclear size and neuronal population of two memory-related diencephalic centres, the mammillary body and the anterior thalamic complex, has been examined in 24 chronic male alcoholics and 22 age-matched male controls. Cases were subdivided into three age groups (30-44 years, 45-59 years and 60-75 years). The results showed a significant reduction in both neuronal numbers and nuclear size in alcoholics compared to controls. Differences were especially high in the youngest alcoholics. The intensity of liver damage (steatosis vs. cirrhosis) did not have any significant effect. Moreover, an age-related decrease of neuronal number and karyometry was seen in controls but not in alcoholics. Our results suggest that chronic alcoholism accelerates the rate of neuronal loss in the mammillary body and anterior thalamic complex to a degree equivalent to aging. Likewise, chronic alcoholism impairs the compensatory increase in neuronal nuclei area seen in normal aging in these same structures. Our findings show that medial diencephalic memory centres are damaged in chronic alcoholism, which may contribute to the clinical symptomatology of these persons.

Quantitative analysis of nanoscale intranuclear structural alterations in hippocampal cells in chronic alcoholism via transmission electron microscopy imaging

Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging. The results, which were obtained at length scales ranging from ~30 to 200 nm, show that 10–12 week-old mice fed a Lieber–DeCarli liquid (alcoholic) diet had a higher degree of structural alteration than control mice fed a normal diet without alcohol. The degree of structural alteration became significantly distinguishable at a sample length of ~100 nm, which is the typical length scale of the building blocks of cells, such as DNA, RNA, proteins and lipids. Interestingly, different degrees of structural alteration at such length scales suggest possible structural rearrangement of chromatin inside the nuclei in chronic alcoholism.

Effects of Chronic Alcoholism on Haematological and Biochemical Parameters in Malwa Belt (Punjab)

Effects of Chronic Alcoholism on Haematological and Biochemical Parameters in Malwa Belt (Punjab)

Alcohol-Induced Increases in Inflammatory Cytokines Are Attenuated by Nicotine in Region-Selective Manner in Male Rats.

BackgroundHeavy use of alcohol is commonly associated with heavy smoking (nicotine intake). Although many factors, including mood effects of these two drugs may contribute to their co-use, the exact neurobiological underpinnings are far from clear. It is well known that chronic alcohol exposure induces neuroinflammation that may precipitate depressive-like behavior, which is considered an important factor in alcohol relapse. Nicotine, on the other hand, possesses anti-inflammatory and antidepressant effects.PurposeIn this study, we sought to determine which proinflammatory markers may be associated with the depressogenic effects of chronic alcohol and whether nicotine pretreatment may normalize these changes.Study designFor this purpose, we treated adult male Wistar rats with alcohol (1.0 g/kg, IP), nicotine (0.3 mg/kg, IP) or their combination once daily for 14 days. Two prominent proinflammatory cytokines (IL-1β and TNF-α) in two primary brain regions, namely the hippocampus and frontal cortex that are intimately involved in mood regulation, were evaluated.ResultsChronic alcohol resulted in increases in both cytokines in both regions as determined by Western blot. Nicotine completely blocked alcohol-induced effects in the hippocampus, but not in the frontal cortex. These data suggest that nicotine may mitigate the inflammatory effects of alcohol in brain-selective region. Hence, the previously observed depressogenic effects of alcohol and the antidepressant effects of nicotine may at least be partially mediated through manipulations of proinflammatory cytokines in the hippocampus.ConclusionThese findings suggest possible therapeutic potential of anti-inflammatory cytokines in combating alcohol-induced depression and/or relapse.