bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lesions of the Extended Amygdala in C57BL/6J Mice Do Not Block the Intermittent Ethanol Vapor‐Induced Increase in Ethanol Consumption
Authors: Dhaher Ronnie , Finn Deborah , Snelling Christopher , Hitzemann Robert 
Published: September 2008

Background:  The central extended amygdala (cEA) which includes the central nucleus of the amygdala (CeA) and the lateral posterior bed nucleus of the stria terminalis (BNSTLP), has been proposed to play a key role in excessive ethanol consumption in humans (Koob and Le Moal, 2005 Nat Neurosci 8:1442). To examine this relationship, we used a murine model of ethanol dependence (Becker and Lopez, 2004 Alcohol Clin Exp Res 28:1829; Lopez and Becker, 2005 Psychopharmacology (Berl) 181:688) and compared animals with sham lesions and electrolytic lesions of the CeA and BNSTLP.Methods:  Male C57BL/6J (B6) mice were first acclimated to a limited‐access 2‐bottle‐choice preference procedure. The access period began 3 hours into the dark phase of the light‐dark cycle and continued for 2 hours. Once acclimated (1 week), mice underwent chronic exposure to and intermittent withdrawal from ethanol vapor. The animals were then retested in the limited‐access 2‐bottle‐choice preference procedure. In some experiments, electrolytic and sham lesions of the CeA or BNSTLP were performed prior to initiating the 2‐bottle choice procedure.Results:  In a series of 5 preliminary experiments, mice were randomly assigned either to the standard intermittent ethanol vapor procedure or to the standard procedure but with air in the vapor chamber (control). The air‐control procedure produced no change in ethanol intake when compared to baseline consumption. In contrast, intermittent ethanol vapor exposure increased ethanol consumption by almost 50%. The increase in consumption was associated with an increase in total fluid volume consumed and no change in ethanol preference. Lesions of both the BNSTLP and CeA significantly decreased baseline ethanol consumption, the former by decreasing fluid consumption and the latter by decreasing ethanol preference. Intermittent ethanol vapor exposure significantly increased consumption in both the BNSTLP‐ and CeA‐lesioned animals, largely by increasing the total volume of fluid consumed.Conclusions:  The results obtained clearly demonstrate that the cEA has a role in the regulation of ethanol consumption in the limited‐access procedure. However, neither lesions of the CeA nor BNSTLP prevented the intermittent ethanol vapor‐induced increase in consumption. These data do not preclude some role of the cEA in the increased ethanol consumption following intermittent ethanol vapor exposure, but would suggest that other brain regions also must have a significant influence.
Effects of Ethanol on Cytokine Production After Surgery in a Murine Model of Gram‐Negative Pneumonia
Authors: Spies Claudia D. , Lanzke Nadine , Schlichting Uwe , Muehlbauer Steffen , Pipolo Carlotta , Von Mettenheim Moritz , Lehmann Anett , Morawietz Lars , Nattermann Herbert , Sander Michael 
Published: September 2008

Background:  Both alcohol abuse and surgery have been shown to impair immune function. The frequency of postoperative infectious complications is 2‐ to 5‐fold increased in long‐term alcoholic patients, leading to prolonged hospital stay. Following surgery, an increase in interleukin (IL)‐6 has been shown to be associated with increased tissue injury and interleukin 1‐(IL‐10) is known to represent an anti‐inflammatory signal. The purpose of this study was to test the hypothesis that several days of excess alcohol consumption results in more pronounced immunosuppression. We assume that alcoholic animals show increased levels of IL‐10 in response to infection and increased IL‐6 due to a more pronounced lung pathology.Methods:  Thirty‐two female Balb/c mice were pretreated with ethanol (EtOH) at a dose of (3.8 mg/g body weight) or saline (NaCl) for 8 days. At day 8 of the experiment all mice underwent a median laparotomy. Two days postsurgery mice were either applicated 104 CFU Klebsiella pneumoniae or received sham‐infection with saline. A total number of 4 groups (EtOH/K. pneumoniae; NaCl/K. pneumoniae; EtOH/Sham‐infection, NaCl/Sham‐infection) was investigated and a clinical score evaluated. Twenty‐four hours later mice were killed; lung, spleen, and liver were excised for protein isolation and histological assessment. IL‐6 and IL‐10 levels were detected by ELISA.Results:  Alcohol‐exposed mice exhibited a worsened clinical appearance. The histological assessment demonstrated a distinct deterioration of the pulmonary structure in alcohol‐treated animals. In the lung, IL‐6 and IL‐10 was significantly increased in alcohol‐exposed infected mice compared to saline‐treated infected mice. The clinical score correlated significantly with IL‐6 (r = 0.71; p < 0.01) and IL‐10 levels (r = 0.64; p < 0.01) in the lung.Conclusions:  Ethanol treatment in this surgical model led to a more severe pulmonary infection with K. pneumoniae which was associated with more tissue destruction and increased levels of IL‐6 and IL‐10 and a worsened clinical score.
Regulation of Motivation to Self‐Administer Ethanol by mGluR5 in Alcohol‐Preferring (P) Rats
Authors: Besheer Joyce , Faccidomo Sara , Grondin Julie J. M. , Hodge Clyde W. 
Published: September 2008

Background:  Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self‐administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement.Methods:  Alcohol‐preferring (P) rats were trained to self‐administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self‐administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance.Results:  The mGluR1 antagonist, 3,4‐dihydro‐2H‐pyrano[2,3]b quinolin‐7‐yl (cis‐4‐methoxycyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6‐methyl‐2‐(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose‐dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity.Conclusions:  Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self‐administer ethanol.
A Comparison of Results From an Alcohol Survey of a Prerecruited Internet Panel and the National Epidemiologic Survey on Alcohol and Related Conditions
Authors: Heeren Timothy , Edwards Erika M. , Dennis J. Michael , Rodkin Sergei , Hingson Ralph W. , Rosenbloom David L. 
Published: September 2008

Background:  Given today’s telecommunications environment, random digit dial (RDD) telephone surveys face declining response rates and coverage, and increasing costs. As an alternative to RDD, we surveyed participants in a randomly recruited standing Internet panel supplemented with a randomly sampled telephone survey of nonpanel members for a study of associations between onset of alcohol use and later alcohol‐related problems. The purpose of this paper was to compare results from our survey with results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a face‐to‐face probability sample survey of 43,093 adults, with a focus on associations between demographics, age of drinking onset, and alcohol dependence.Methods:  Demographic and drinking characteristics from our survey of 4,021 ever‐drinkers between the ages of 18 and 39 years were compared with the characteristics of 11,549 similarly aged ever‐drinkers from the NESARC. Weighted analyses accounting for sampling design compared these 2 samples on drinking characteristics over the past year and during a respondent’s heaviest period of drinking, and in multivariate models examining associations between demographics, age of drinking onset, and lifetime alcohol dependence.Results:  Participants in the supplemented Internet panel were similar to the national population of 18‐ to 39‐year‐old ever drinkers on gender, education, and race/ethnicity, while adults who were aged 18 to 25 years were under‐represented in the Internet panel. The supplemented Internet panel reported higher rates of moderate risk drinking over the past 12 months, lifetime high‐risk drinking, and lifetime (ever) alcohol dependence. Estimates of the associations between alcohol dependence and age of drinking onset, risky drinking, and family history of alcohol problems did not significantly differ between the supplemented Internet sample and the NESARC survey.Conclusions:  Randomly recruited Internet‐based panels may provide an alternative to random digit dial telephone surveys and in‐person surveys for some studies of factors associated with alcohol‐related problems.
The Reinforcing Properties of Salsolinol in the Ventral Tegmental Area: Evidence for Regional Heterogeneity and the Involvement of Serotonin and Dopamine
Authors: Rodd Zachary A. , Oster Scott M. , Ding Zheng‐Ming , Toalston Jamie E. , Deehan Gerald , Bell Richard L. , Li Ting‐Kai , McBride William J. 
Published: September 2008

Background:  Salsolinol (SAL), the condensation product of acetaldehyde and dopamine, may be a factor contributing to alcohol abuse. Previous research indicated that both ethanol and acetaldehyde are self‐administered into the posterior ventral tegmental area (VTA). The current study examined SAL self‐infusions into the VTA, and determined the involvement of dopamine neurons and 5‐HT3 receptors in this process.Methods:  The intracranial self‐administration technique was used to determine the self‐infusion of SAL into the VTA of adult, male Wistar rats. The rats were placed in 2‐lever (active and inactive) experimental chambers, and allowed to respond for the self‐infusion of 0, 0.03, 0.1, 0.3, 1.0 or 3.0 μM SAL into the posterior or anterior VTA. In a second experiment, rats self‐administered 0.3 μM SAL for the initial 4 sessions, co‐administered SAL with ICS‐205,930 (a 5‐HT3 receptor antagonist) or quinpirole (a D2,3 receptor agonist) for sessions 5 and 6, and then only 0.3 μM SAL for session 7.Results:  Wistar rats, given 0.03 to 0.3 μM SAL, received more infusions per session than did the group given artificial cerebrospinal fluid (aCSF) alone (e.g., 41 infusions for 0.1 μM SAL versus 9 infusions for the aCSF group), and responded more on the active than inactive lever. These effects were observed in the posterior but not in anterior VTA. Co‐infusion of 100 μM ICS‐205,930, or quinpirole significantly reduced self‐infusions and active lever responding.Conclusions:  SAL produces reinforcing effects in the posterior VTA of Wistar rats, and these effects are mediated by activation of DA neurons and local 5‐HT3 receptors.
The CRF‐1 Receptor Antagonist, CP‐154,526, Attenuates Stress‐Induced Increases in Ethanol Consumption by BALB/cJ Mice
Authors: Lowery Emily G. , Sparrow Angela M. , Breese George R. , Knapp Darin J. , Thiele Todd E. 
Published: September 2008

Background:  Corticotropin‐releasing factor (CRF) signaling modulates neurobiological responses to stress and ethanol, and may modulate observed increases in ethanol consumption following exposure to stressful events. The current experiment was conducted to further characterize the role of CRF1 receptor (CRF1R) signaling in stress‐induced increases in ethanol consumption in BALB/cJ and C57BL/6N mice.Methods:  Male BALB/cJ and C57BL/6N mice were given continuous access to 8% (v/v) ethanol and water for the duration of the experiment. When a baseline of ethanol consumption was established, animals were exposed to 5 minutes of forced swim stress on each of 5 consecutive days. Thirty minutes before each forced swim session, animals were given an intraperitoneal injection of a 10 mg/kg dose of CP‐154,526, a selective CRF1R antagonist, or an equal volume of vehicle. The effect of forced swim stress exposure on consumption of a 1% (w/v) sucrose solution was also investigated in an ethanol‐naïve group of BALB/cJ mice.Results:  Exposure to forced swim stress significantly increased ethanol consumption by the BALB/cJ, but not of the C57BL/6N, mice. Stress‐induced increases in ethanol consumption were delayed and became evident approximately 3 weeks after the first stressor. Additionally, forced swim stress did not cause increases of food or water intake and did not promote delayed increases of sucrose consumption. Importantly, BALB/cJ mice pretreated with the CRF1R antagonist showed blunted stress‐induced increases in ethanol intake, and the CRF1R antagonist did not influence the ethanol drinking of non‐stressed mice.Conclusions:  The present results provide evidence that CRF1R signaling modulates the delayed increase of ethanol consumption stemming from repeated exposure to a stressful event in BALB/cJ mice.
Key Role of Ethanol‐Derived Acetaldehyde in the Motivational Properties Induced by Intragastric Ethanol: A Conditioned Place Preference Study in the Rat
Authors: Peana Alessandra T. , Enrico Paolo , Assaretti Anna Rita , Pulighe Elena , Muggironi Giulia , Nieddu Maria , Piga Antonio , Lintas Alessandra , Diana Marco 
Published: September 2008

Background:  Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), is produced peripherally by gastric and hepatic alcohol dehydrogenase (ADH) and centrally by brain catalase. In spite of the aversive properties classically ascribed to ACD, it has recently been suggested that ACD might mediate some of the motivational effects of EtOH. Accordingly, the relative role of ACD in the positive motivational properties of EtOH ingested is increasingly becoming the matter of debate. Thus, we studied the ability of intragastrically administered EtOH, ACD and EtOH‐derived ACD to induce conditioned place preference (cpp) in rats.Methods:  Wistar rats were pretreated intraperitoneally with saline, the peripheral competitive inhibitor of ADH, 4‐methylpyrazole (4‐MP, 22.5, 45 or 67.5 mg/kg) or with the selective ACD‐sequestrating agent, d‐penicillamine (DP, 25 or 50 mg/kg), before the intragastric administration of saline, EtOH (0.5, 1 or 2 g/kg) or ACD (10, 20, or 40 mg/kg). The specificity of 4‐MP and DP effects was addressed using morphine‐induced cpp (2.5 mg/kg).Results:  Both, EtOH and ACD dose‐dependently induced cpp; further, while EtOH‐induced cpp was prevented by the administration of 4‐MP and by DP, ACD‐induced cpp was unaltered by 4‐MP administration and prevented by DP. Both pretreatments did not interfere with morphine‐induced cpp indicating that 4‐MP and DP specifically modulate the motivational properties of EtOH and ACD.Conclusion:  The ability of 4‐MP and DP to decrease EtOH‐induced cpp suggests that a reduction of ACD levels is crucial in depriving EtOH from its motivational properties as indexed by the cpp procedure. In addition, this conclusion is supported by the inefficacy of 4‐MP in preventing ACD‐induced cpp, and by its blockade observed after administration of the selective ACD sequestrating agent DP. The present results underscore the role of EtOH‐derived ACD in EtOH‐induced motivational properties as well as its abuse liability.
Blockade of the Corticotropin Releasing Factor Type 1 Receptor Attenuates Elevated Ethanol Drinking Associated With Drinking in the Dark Procedures
Authors: Sparta Dennis R. , Sparrow Angela M. , Lowery Emily G. , Fee Jon R. , Knapp Darin J. , Thiele Todd E. 
Published: September 2008

Background: Drinking in the dark (DID) procedures have recently been developed to induce high levels of ethanol drinking in C57BL/6J mice, which result in blood ethanol concentrations (BECs) reaching levels that have measurable affects on physiology and/or behavior. The present experiments determined whether the increased ethanol drinking caused by DID procedures can be attenuated by pretreatment with CP‐154,526; a corticotropin releasing factor type‐1 (CRF1) receptor antagonist.Methods: In Experiment 1, male C57BL/6J mice received ethanol (20% v/v) in place of water for 4 hours, beginning with 3 hours into the dark cycle. On the fourth day, mice were given an intraperitoneal injection of one of the 4 doses of CP‐154,526 (0, 1, 3, 10 mg/kg) 30 minutes before receiving their ethanol bottle. In Experiment 2, C57BL/6J mice had 2 hours of access to the 20% ethanol solution, beginning with 3 hours into the dark cycle on days 1 to 3, and 4 hours of access to the ethanol bottle on day 4 of DID procedures. Mice were given an intraperitoneal injection of one of the 4 doses of CP‐154,526 (0, 1, 3, 10 mg/kg) 30 minutes before receiving their ethanol bottle on day 4. Tail blood samples were collected immediately after the 4‐hour ethanol access period on the fourth day of each experiment. Additional control experiments assessed the effects of CP‐154,526 on 4‐hour consumption of a 10% (w/v) sucrose solution and open‐field locomotor activity.Results: In Experiment 1, the vehicle‐treated group consumed approximately 4.0 g/kg/4 h of ethanol and achieved BECs of approximately 30 mg%. Furthermore, pretreatment with the CRF1receptor antagonist did not alter ethanol consumption. On the other hand, procedures used in Experiment 2 resulted in vehicle‐treated mice consuming approximately 6.0 g/kg/4 h of ethanol with BECs of about 80 mg%. Additionally, the 10 mg/kg dose of CP‐154,526 significantly reduced ethanol consumption and BECs to approximately 3.0 g/kg/4 h and 27 mg%, respectively, relative to vehicle‐treated mice. Importantly, the 10 mg/kg dose of the CRF1R antagonist did not significantly alter 4‐hour sucrose consumption or locomotor activity.Conclusions: These data indicate that CRF1R signaling modulates high, but not moderate, levels of ethanol drinking associated with DID procedures.
Acculturation, Drinking, and Alcohol Abuse and Dependence Among Hispanics in the Texas–Mexico Border
Authors: Caetano Raul , Ramisetty‐Mikler Suhasini , Wallisch Lynn S. , McGrath Christine , Spence Richard T. 
Published: September 2008

Background: Acculturation has been linked to an increased prevalence of alcohol‐related problems. However, most of the research has been conducted with Hispanic populations in metropolitan areas of the United States, none of which is on the U.S.–Mexico border. This study examines the association between acculturation, heavy episodic drinking, and DSM‐IV alcohol abuse and dependence among Hispanics in the Texas–Mexico border.Methods: The study used data from a survey conducted (2002 to 2003) along the Texas–Mexico border and included 472 male and 484 female Hispanic adults from El Paso, the Rio Grande Valley, and colonias. Based on the Acculturation Rating Scale for Mexican Americans‐II scale, respondents were coded into 4 acculturation categories: “very Mexican oriented,”“Mexican bicultural,”“Anglo bicultural,” or “very Anglo/Anglicized.”.Results: Acculturation was related to lower rates of alcohol use disorders among men and a higher frequency of heavy episodic drinking among women. Multivariate analyses indicate that men who report heavy episodic drinking and those who are “very Mexican,”“bicultural Mexican,” or “bicultural Anglo” are more at higher risk for alcohol abuse and/or dependence compared with “very Anglo/Anglicized” men. For women, acculturation level did not predict alcohol disorders. Statistical analyses included testing for bivariate associations and multivariate logistic regression predicting heavy episodic drinking alcohol abuse or dependence.Conclusions: This study suggests that acculturation has different effects on drinking for men and women. This finding needs some attention as literature also indicates that women drink more and may develop more alcohol‐related problems as they acculturate. This increase in women’s drinking is probably because of U.S. society’s more liberal norms governing female drinking. The “bimodal” distribution of risk, in which only men in “very Anglo” group are at a lower risk than the others, may be unique to the Border. The association between acculturation and alcohol use disorders does not appear to be linear and the effect of acculturation is not uniform on individuals’ drinking behavior.
Decreased Immunoreactivity of the Melanocortin Neuropeptide α‐Melanocyte‐Stimulating Hormone (α‐MSH) After Chronic Ethanol Exposure in Sprague–Dawley Rats
Authors: Navarro Montserrat , Cubero Inmaculada , Knapp Darin J. , Breese George R. , Thiele Todd E. 
Published: September 2008

Background: The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor proopiomelanocortin (POMC). Recent pharmacologic and genetic evidence suggests that MC receptor (MCR) signaling modulates neurobiologic responses to ethanol and ethanol intake. Because ethanol decreases POMC mRNA levels, we determined if exposure to an ethanol‐containing diet (ED) would significantly reduce central immunoreactivity of the MC peptide α‐MSH in rats. We also determined if ethanol exposure would alter the immunoreactivity of agouti‐related protein (AgRP), an endogenous MCR antagonist.Methods: Male Sprague–Dawley rats were given 18 days of access to normal rodent chow or a control diet (CD), or short‐term (4 days) or long‐term (18 days) access to an ED. At the end of the study, rats were perfused with 4% paraformaldehyde and their brains were sectioned into two sets for processing with α‐MSH or AgRP immunohistochemistry.Results: Rats exposed to an ED showed significant reductions of central α‐MSH immunoreactivity relative to rats exposed to a control diet (CD) or normal rodent chow. Ethanol‐induced reductions of α‐MSH immunoreactivity were site‐specific and were noted in regions of the hypothalamus and extended amygdala, as well as the paraventricular nucleus of the thalamus. Because there were no differences in body weights or caloric intake between the CD and ED groups, reductions of α‐MSH immunoreactivity in ED‐treated rats are best explained by ethanol exposure rather than altered energy balance. No significant ethanol‐induced alterations in hypothalamic AgRP immunoreactivity were detected.Conclusions: The present study shows that ethanol site specifically reduces α‐MSH immunoreactivity in rat brain. These observations, in tandem with recent pharmacologic and genetic studies, suggest that the endogenous MC system modulates neurobiologic responses to ethanol. Thus, compounds which target MCRs may prove to have therapeutic value in the treatment of excessive ethanol consumption and/or the symptoms associated with ethanol withdrawal.