Alcohol最新文献

{"title":"Assessment of reduction in stimulus generalization of ethanol-seeking during recovery: A rapid procedure","authors":"Hanana AlTfaili,&nbsp;R.J. Lamb,&nbsp;Brett C. Ginsburg","doi":"10.1016/j.alcohol.2024.09.003","DOIUrl":"10.1016/j.alcohol.2024.09.003","url":null,"abstract":"<div><div>Previously, we developed a procedure which showed that longer histories of reinforced alternative behavior decrease the risk of relapse caused by a range of stimuli which had previously occasioned drinking. The decrease in relapse risk was likely due to a decrease in attention to the stimuli over the course of repeated engagement in the alternative behavior. However, this previous procedure was time consuming and did not mirror the procedure we used to observe changes in relapse risk. This study aimed at replicating the previous relationship between the duration of engaging in an alternative behavior and shift in stimulus generalization for drinking using a procedure that allows longitudinal analysis over time and is consistent with other procedures we have developed. Rats were trained to respond for ethanol in the presence of one stimulus (16 kHz tone; food Fixed Ratio (FR)150 and ethanol FR5), and for food in the under another stimulus (8 kHz tone; food and ethanol FR5). Then, recovery-like sessions with food predominant responding occurred in the presence of only the low-cost food stimulus. During these sessions, rats were exposed to non-reinforced graded stimuli alternation from 8 to 16 kHz alternating with the reinforced low-cost food stimulus. The number of responses on each (food and ethanol) lever before completing 5 responses on either lever was the main measure. Consistent with the earlier procedure, the current procedure showed that graded variation of tone from 8 to 16 kHz produced a graded increase in responding for ethanol compared to responding for food. In addition, longer periods of engaging in recovery-like responding shift the generalization function downwards. This procedure confirms the earlier pattern of stimulus generalization over longer periods of behavior consistent with recovery. This strengthens our hypothesis that shifts in attention to alcohol-related stimuli are important to the development of relapse resistance during recovery.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 161-167"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of social vulnerability index on patients with alcohol-related liver disease","authors":"Ayushi Jain ,&nbsp;Michael R. Wellner ,&nbsp;Jing Peng ,&nbsp;Jianing Ma ,&nbsp;Kenneth D. Allen ,&nbsp;Chelsey McShane ,&nbsp;Mitchell L. Ramsey ,&nbsp;Khalid Mumtaz ,&nbsp;Sean G. Kelly ,&nbsp;Lanla F. Conteh ,&nbsp;Robert Kirkpatrick ,&nbsp;Lindsay A. Sobotka","doi":"10.1016/j.alcohol.2024.08.005","DOIUrl":"10.1016/j.alcohol.2024.08.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Alcohol related liver disease (ALD) affects diverse communities with individual and social characteristics that can impact outcomes. The social vulnerability index (SVI) assigns a score between 0 and 1, where higher scores represent an increased risk of social vulnerability. We sought to assess the impact of SVI on outcomes of patients hospitalized with ALD with access to social support services.</div></div><div><h3>Methods and materials</h3><div>Hospitalizations for ALD at our institution between March and August 2019 were reviewed. All patients were assigned an SVI score based on their residential census tract. Per our standard practice, patients were screened by care coordinators to identify needs for rehabilitation counseling, and care coordination after discharge. Demographics, hepatic decompensation, critical care needs, readmission, and mortality were compared.</div></div><div><h3>Results</h3><div>Among 73 patients admitted for alcoholic hepatitis, 32 had a low SVI and 42 had a high SVI. African American patients were more likely to have a higher SVI (35% vs 0%, p=&lt;0.001). No significant difference in outcomes based on SVI was noted.</div><div>There were 393 patients admitted for alcoholic cirrhosis including 166 with a low SVI and 227 with a high SVI. Patients that were African American (23.6% vs 5.5%, p=&lt;0.001) or disabled (41.4% vs 29.5%, p = 0.008) had a higher SVI. No significant difference in outcomes based on SVI was noted.</div></div><div><h3>Conclusion</h3><div>Most patients admitted for ALD had a high SVI; however, SVI did not impact hospitalization outcomes.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 147-150"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel alcohol+nicotine co-use self-administration procedure reveals sex differences and differential alteration of mesocorticolimbic TLR- and cholinergic-related neuroimmune gene expression in rats","authors":"Christie A. Randall ,&nbsp;Dongxiao Sun ,&nbsp;Patrick A. Randall","doi":"10.1016/j.alcohol.2024.08.003","DOIUrl":"10.1016/j.alcohol.2024.08.003","url":null,"abstract":"<div><p>Although alcohol and nicotine are two of the most commonly co-used drugs with upwards of 90% of adults with an alcohol use disorder (AUD) in the US also smoking, we don't tend to study alcohol and nicotine use this way. The current studies sought to develop and assess a novel alcohol + nicotine co-access self-administration (SA) model in adult male and female Long-Evans rats. Further, both drugs are implicated in neuroimmune function, albeit in largely opposing ways. Chronic alcohol use increases neuroinflammation via toll-like receptors (TLRs) which in turn increases alcohol intake. By contrast, nicotine produces anti-inflammatory effects, in part, through the monomeric alpha7 receptor (ChRNa7). Following long-term co-access (6 months), rats reliably administered both drugs during daily sessions, however males generally responded for more alcohol and females for nicotine. This was reflected in plasma analysis with translationally relevant intake levels of both alcohol and nicotine, making it invaluable in studying the effects of co-use on behavior and CNS function. Moreover, male rats show sensitivity to alterations in alcohol concentration whereas females show sensitivity to alterations in nicotine concentration. Rats trained on this procedure also developed an anxiogenic phenotype. Finally, we assessed alterations in neuroimmune-related gene expression in the medial prefrontal cortex – prelimbic, (mPFC-PL), nucleus accumbens core (AcbC), and ventral tegmental area (VTA). In the AcbC, where α7 expression was increased and β2 was decreased, markers of pro-inflammatory activity were decreased, despite increases in TLR gene expression suggesting that co-use with nicotine modulates inflammatory state downstream from the receptor level. By contrast, in mPFC-PL where α7 was not increased, both TLRs and downstream proinflammatory markers were increased. Taken together, these findings support that there are brain regional and sex differences with co-use of alcohol + nicotine SA and suggest that targeting nicotinic α7 may represent a novel strategy for treating alcohol + nicotine co-dependence.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 115-131"},"PeriodicalIF":2.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0741832924001150/pdfft?md5=e1355ae20beb527810f3ef20e0cc2fef&pid=1-s2.0-S0741832924001150-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of moderate prenatal alcohol exposure on performance in hippocampal-sensitive spatial memory and anxiety tasks by adult male and female rat offspring","authors":"Gabriela Acosta ,&nbsp;Kehiry Trejo Rico ,&nbsp;John T. Madden ,&nbsp;Ariyana LaCour ,&nbsp;Enhui Wang ,&nbsp;Lilliana M. Sanchez ,&nbsp;Suzy Davies ,&nbsp;Carlos Maestas-Olguin ,&nbsp;Kayla B. Cox ,&nbsp;Nicole C. Reyna ,&nbsp;Jeremy Hogeveen ,&nbsp;Daniel D. Savage ,&nbsp;Nathan S. Pentkowski ,&nbsp;Benjamin J. Clark","doi":"10.1016/j.alcohol.2024.08.002","DOIUrl":"10.1016/j.alcohol.2024.08.002","url":null,"abstract":"<div><p>Moderate prenatal alcohol exposure (mPAE) results in structural alterations to the hippocampus. Previous studies have reported impairments in hippocampal-sensitive tasks, but have not compared performance between male and female animals. In the present study, performance in hippocampal-sensitive spatial memory and anxiety behavior tests were compared across adult male and female saccharin (SACC) control mPAE Long-Evans rat offspring. Two tests of spatial memory were conducted that were aimed at assessing memory for recently acquired spatial information: A delayed spatial alternation task using an M-shaped maze and a delayed match-to-place task in the Morris water task. In both tasks, rats in SACC and mPAE groups showed similar learning and retention of a spatial location even after a 2-h interval between encoding and retention. A separate group of adult male and female SACC and mPAE rat offspring were tested for anxiety-like behaviors in the elevated plus-maze paradigm. In this test, both male and female mPAE rats exhibited a significantly greater amount of time and a greater number of head dips in the open arms, while locomotion and open arm entries did not differ between groups. The results suggest that mPAE produces a reduction in anxiety-like behaviors in both male and female rats in the elevated plus-maze.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 75-86"},"PeriodicalIF":2.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol-induced fibroblast growth factor 21 secretion is increased in individuals with alcohol use disorder","authors":"Amalie R. Lanng ,&nbsp;Lærke S. Gasbjerg ,&nbsp;Andrea I.F. Sucksdorff ,&nbsp;Jens S. Svenningsen ,&nbsp;Tina Vilsbøll ,&nbsp;Matthew P. Gillum ,&nbsp;Filip K. Knop","doi":"10.1016/j.alcohol.2024.08.001","DOIUrl":"10.1016/j.alcohol.2024.08.001","url":null,"abstract":"<div><h3>Background</h3><p>Alcohol use disorder (AUD) affects 5% of the global population. Despite its high prevalence, the pathophysiology of AUD remains enigmatic, hindering the development of novel therapeutics. Interestingly, the liver hormone fibroblast growth factor 21 (FGF21), which is currently in late-stage clinical trials for the treatment of non-alcoholic steatohepatitis, has been implicated by recent genome-wide association studies as a regulator of alcohol consumption.</p></div><div><h3>Methods</h3><p>This study aimed to evaluate plasma responses of FGF21 to an alcohol challenge in three groups: 15 males with AUD, 15 healthy males with a father with AUD (Predisposed), and 15 healthy males without any predisposition to AUD (Controls). All participants were investigated after an overnight fast. Assessments, including blood sampling and visual analog scale-assessed desire for alcohol intake, were performed before and for 10 h after ingesting 0.5 g alcohol per kg body weight over 10 min.</p></div><div><h3>Results</h3><p>The three groups were age and body-mass index-matched and had normal plasma concentrations of transaminases and FibroScan®-assessed elastography. Baseline FGF21 concentrations did not differ between groups, but individuals with AUD exhibited greater FGF21 responses to alcohol (area under the curve (AUC_0–600 min): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC_0–600 min: 453 ± 333 ng/ml × min, <em>P</em> = 0.03) but not Predisposed (AUC_0–600 min: 556 ± 429 ng/ml × min, <em>P</em> = 0.11).</p></div><div><h3>Conclusion</h3><p>In conclusion, we demonstrate greater alcohol-induced FGF21 responses in individuals with AUD compared to healthy individuals without paternal predisposition to AUD, suggesting a role for FGF21 in AUD pathophysiology.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 69-74"},"PeriodicalIF":2.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0741832924001125/pdfft?md5=4c41d86367cd092ec5e9a21468750d4b&pid=1-s2.0-S0741832924001125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol hangover versus dehydration revisited: The effect of drinking water to prevent or alleviate the alcohol hangover","authors":"Marlou Mackus ,&nbsp;Ann-Kathrin Stock ,&nbsp;Johan Garssen ,&nbsp;Andrew Scholey ,&nbsp;Joris C. Verster","doi":"10.1016/j.alcohol.2024.07.006","DOIUrl":"10.1016/j.alcohol.2024.07.006","url":null,"abstract":"<div><p>The alcohol hangover is a combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero. A popular theory suggests that dehydration is the primary cause of alcohol hangover and that the consumption of water could alleviate hangover symptoms. Here, the current evidence on the relationship between hangover severity, thirst, and water consumption is summarized. The positive correlations of the amount of water consumed with both hangover severity and thirst suggest that both dehydration and the hangover are co-occurring after-effects of alcohol consumption. While hangovers were typically relatively enduring, dehydration effects were usually mild and short-lasting. Survey data revealed that water consumption during or directly after alcohol consumption had only a modest effect in preventing next-day hangover. Also, the amount of water consumed during hangover was not related to changes of hangover severity and thirst. Thus, water consumption was not effective to alleviate the alcohol hangover. Taken together, these data suggests that alcohol hangover and dehydration are two co-occurring but independent consequences of alcohol consumption.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 9-18"},"PeriodicalIF":2.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0741832924001009/pdfft?md5=e94a0c20b238385159f92ce792f17495&pid=1-s2.0-S0741832924001009-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging pharmacological targets for alcohol use disorder","authors":"Dakota F. Brockway ,&nbsp;Nicole A. Crowley","doi":"10.1016/j.alcohol.2024.07.007","DOIUrl":"10.1016/j.alcohol.2024.07.007","url":null,"abstract":"<div><p>Alcohol Use Disorder (AUD) remains a challenging condition with limited effective treatment options; however new technology in drug delivery and advancements in pharmacology have paved the way for discovery of novel therapeutic targets. This review explores emerging pharmacological targets that offer new options for the management of AUD, focusing on the potential of somatostatin (SST), vasoactive intestinal peptide (VIP), glucagon-like peptide-1 (GLP-1), nociceptin (NOP), and neuropeptide S (NPS). These targets have been selected based on recent advancements in preclinical and clinical research, which suggest their significant roles in modulating alcohol consumption and related behaviors. SST dampens cortical circuits, and targeting both the SST neurons and the SST peptide itself presents promise for treating AUD and various related comorbidities. VIP neurons are modulated by alcohol and targeting the VIP system presents an unexplored avenue for addressing alcohol exposure at various stages of development. GLP-1 interacts with the dopaminergic reward system and reduces alcohol intake. Nociceptin modulates mesolimbic circuitry and agonism and antagonism of nociceptin receptor offers a complex but promising approach to reducing alcohol consumption. NPS stands out for its anxiolytic-like effects, particularly relevant for the anxiety associated with AUD. This review aims to synthesize the current understanding of these targets, highlighting their potential in developing more effective and personalized AUD therapies, and underscores the importance of continued research in identifying and validating novel targets for treatment of AUD and comorbid conditions.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 103-114"},"PeriodicalIF":2.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0741832924001010/pdfft?md5=ed4817e2024e0fe27707246dadd04f13&pid=1-s2.0-S0741832924001010-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and sobriety: Human brain structure and function in AUD abstinence","authors":"Nicole L. Zabik ,&nbsp;Jennifer Urbano Blackford","doi":"10.1016/j.alcohol.2024.07.003","DOIUrl":"10.1016/j.alcohol.2024.07.003","url":null,"abstract":"<div><p>Women are drinking alcohol as much as men for the first time in history. Women experience more health-related consequences from alcohol use disorder (AUD), like increased prevalence of alcohol-related cancers, faster progression of alcohol-related liver disease, and greater risk for relapse compared to men. Thus, sex differences in chronic alcohol use pose a substantial public health problem. Despite these evident sex differences, our understanding of how these differences present during alcohol abstinence is limited. Investigations of brain structure and function are therefore critical for disentangling factors that lead to sex differences in AUD abstinence. This review will discuss current human neuroimaging data on sex differences in alcohol abstinence, focusing on structural and functional brain measures. Current structural imaging literature reveals that abstinent men have smaller gray and white matter volume and weaker structural connectivity compared to control men. Interestingly, abstinent women do not show differences in brain structure when compared to controls; instead, abstinent women show a relation between alcohol use and decreased measures of brain structure. Current functional brain studies reveal that abstinent men exhibit greater brain activation and stronger task-based functional connectivity to aversive stimuli than control men, while abstinent women exhibit lesser brain activation and weaker task-based functional connectivity than control women. Together, the current literature suggests that sex differences persist well into alcohol abstinence and impact brain structure and function differently. Understanding how men and women differ during alcohol abstinence can improve our understanding of sex-specific effects of alcohol, which will be critical to augment treatment methods to better serve women.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 33-44"},"PeriodicalIF":2.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Mouse Models of Voluntary Alcohol Drinking and Abstinence-Induced Negative Emotion","authors":"Amanda L. Salazar,&nbsp;Samuel W. Centanni","doi":"10.1016/j.alcohol.2024.07.004","DOIUrl":"10.1016/j.alcohol.2024.07.004","url":null,"abstract":"<div><p>Alcohol Use Disorder (AUD) is a growing problem worldwide, causing an incredible burden on health and the economy. Though AUD impacts people of all backgrounds and demographics, increasing evidence has suggested robust sex differences in alcohol drinking patterns and AUD-induced negative emotionality or hyperkatifeia. Rates of problematic drinking have significantly risen among women, and women face more severe negative emotional consequences in abstinence such as increased risk of comorbidity with an anxiety or mood disorder and more severe symptoms of depression. As such, a bevy of preclinical literature using contingent methods of alcohol (ethanol) consumption has amassed in recent years to better understand sex as a biological variable in alcohol drinking and abstinence-induced negative emotionality. Mice are widely used to model alcohol drinking, as they are conducive to genetic manipulation strategies, and many strains will voluntarily consume alcohol. Sex-specific results from these mouse studies, however, have been inconsistent. Therefore, this review aims to summarize the current knowledge on sex differences in AUD-related contingent ethanol drinking and abstinence-induced negative emotionality in mice. Various contingent mouse drinking models and negative emotional-based behavioral paradigms are introduced and subsequently discussed in the context of sex differences to show increasing indications of sex specificity in mouse preclinical studies of AUD. With this review, we hope to inform future research on potential sex differences in preclinical mouse models of AUD and provide mounting evidence supporting the need for more widespread inclusion of preclinical female subjects in future studies.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 45-57"},"PeriodicalIF":2.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interneuron-selective HCN channel knockdown in prelimbic cortex of female rats mimics effects of chronic ethanol exposure","authors":"Benjamin A. Hughes ,&nbsp;Todd K. O'Buckley ,&nbsp;Giorgia Boero ,&nbsp;A. Leslie Morrow","doi":"10.1016/j.alcohol.2024.07.005","DOIUrl":"10.1016/j.alcohol.2024.07.005","url":null,"abstract":"<div><p>Our laboratory has previously shown that chronic ethanol exposure elicits enhanced working memory performance in female, but not male, adult Sprague–Dawley rats, indicative of a fundamental sex difference in cortical plasticity. Recent studies have furthermore revealed that females display markedly reduced HCN-mediated channel activity in inhibitory Martinotti interneurons after chronic ethanol exposure that is similarly not observed in males. From these observations we hypothesized that alcohol induces facilitated working memory performance via down-regulation of these channels’ activity specifically within interneurons. To test this hypothesis, we employed a Pol-II compatible shRNA expression system to elicit targeted knockdown of HCN channel activity in these cells, and measured performance on a delayed Non-Match-to-Sample (NMS) T-maze test to gauge effects on working memory performance. A significant baseline enhancement of working memory performance with HCN channel knockdown was observed, indicative of a critical role for interneuron-expressed HCNs in maintaining optimal cortical network activity during cognitively-demanding tasks. Consistent with previous observations, ethanol exposure resulted in enhanced NMS T-maze performance, however elevated working memory performance was observed in both <em>scram-</em> and <em>hcn-</em>shRNA infected groups after alcohol administration. We therefore conclude that interneuron-expressed HCN channels, despite representing a minor population of total cortical HCN expression, contribute substantially to maintaining working memory processes. Downregulated HCN channel activity, though, does not alone appear sufficient to manifest alcohol-induced enhancement of working memory performance observed in female rats during acute withdrawal.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"121 ","pages":"Pages 59-67"},"PeriodicalIF":2.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}