bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls: Prediction of Alcohol Cue‐Induced Craving?
Authors: Petrakis Ismene L. , Trevisan Louis , D'Souza Cyril , Gil Roberto , Krasnicki Susan , Webb Elizabeth , Heninger George , Cooney Ned , Krystal John H. 
Published: May 2006

Background: Abnormalities in central neurotransmitter systems have been described in alcohol‐dependent individuals and may contribute to alcohol craving. This study compared cerebrospinal fluid (CSF) levels of monoamine metabolites and beta endorphin levels in samples from early‐onset alcohol‐dependent patients (n= 20), late‐onset alcohol‐dependent patients (n= 14), and healthy controls (n= 23). It also evaluated whether these CSF measures levels predicted the degree of craving experienced in response to an alcohol cue. Methods: Individuals meeting DSM‐III and ‐IV R‐criteria for alcohol dependence, 1 to 3 months postdetoxification, and healthy controls underwent a lumbar puncture. Patients also completed a cue exposure test day between 3 and 15 days later. Results: Alcohol‐dependent patients had lower CSF levels of the norepinephrine metabolite MHPG compared with the healthy subjects, but this difference disappeared when differences in age between the groups were accounted for. No other group comparisons between patients and healthy subjects reached significance. CSF levels of the dopamine metabolite HVA were significantly higher in the early‐onset patients compared with the late‐onset patients and controls. The CSF measures did not predict the precue levels of craving, or the increase in craving after alcohol cue exposure. Conclusions: These results are inconclusive about the role of monoaminergic dysregulation in recovering alcoholics. They also question the utility of these CSF measures to predict alcohol cue reactivity in patients who have been sober at least 1 month.
Clozapine's Effects on Ethanol's Motivational Properties
Authors: Thrasher Michael J. , Freeman Pierre A. , Risinger Fred O. 
Published: May 2006

Background: Although dopamine D1 and D2 receptors have been implicated in ethanol's motivational effects, little is known about the contribution of dopamine D4 receptors. The present experiments examined the effects of clozapine, a dopamine D4 receptor antagonist, on ethanol's aversive, rewarding, stimulant, and reinforcing properties. Methods: For taste conditioning, adult male Swiss‐Webster mice received five conditioning trials consisting of 1‐hr access to 0.2 M NaCl. After NaCl access on trials 1‐4, subjects received clozapine (0,1, or 2 mg/kg) followed 30 min later by 0,2, or 4 g/kg ethanol. For place conditioning, Swiss‐Webster mice received six pairings of a tactile stimulus with ethanol (2 g/kg, intraperitoneally), clozapine (1 mg/kg, intraperitoneally) + ethanol, or clozapine alone. Locomotor activity in a 30‐min test was determined in Swiss‐Webster mice receiving 0,0.5, or 1.0 mg/kg clozapine and 0,1, or 2 g/kg ethanol. In a drinking study, separate groups of adult male C57BL/6J mice were allowed 30‐min access to either 10% v/v ethanol mixed in 10% w/v sucrose or 10% sucrose without ethanol. During testing, both groups were given 0 or 1 mg/kg clozapine 30 min before fluid access. Results: Ethanol flavor pairings during taste conditioning reduced subsequent flavor intakes, indicating the development of conditioned taste aversion. Clozapine reduced the magnitude of 4 g/kg ethanol‐conditioned aversion only on trial 4 at the 2 mg/kg dose. Conditioned place preference for the ethanol‐paired stimulus was not altered by clozapine. Clozapine alone did not produce either conditioned preference or aversion. Ethanol‐stimulated activity was reduced by clozapine treatment. However, clozapine alone did not alter locomotor activity levels. Clozapine reduced sucrose consumption but did not alter ethanol/sucrose intake. Conclusions: These data suggest that clozapine influences a limited range of ethanol‐motivated behaviors. Specifically, dopamine D4 receptors appear important for ethanol's stimulant effect and possibly ethanol aversion, but not ethanol reward and reinforcement.
Alcohol Deprivation Effect Is Prolonged in the Alcohol Preferring (P) Rat After Repeated Deprivations
Authors: Rodd‐Henricks Zachary A. , McKinzie David L. , Shaikh Saame R. , Murphy James M. , McBride William J. , Lumeng Lawrence , Li Ting‐Kai 
Published: May 2006

Background:The alcohol deprivation effect (ADE) is a temporary increase in the ratio of ethanol/total fluid intake and the voluntary intake of ethanol solutions over baseline drinking conditions when ethanol access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. The current study examined the effects of initial deprivation length and number of deprivation exposures on the ADE in alcohol‐preferring (P) rats.Methods:Adult female P rats received 24‐hr free‐choice access to 10% (v/v) ethanol and water for 6 weeks. Rats were then randomly assigned to five groups deprived of ethanol for O (control), 2, 4, 6, or 8 weeks (W). All deprived groups were then given 24‐hr access to ethanol for 2 weeks before bbeing deprived of ethanol for another 2 weeks.Results:After the initial ethanol deprivation period, the deprived groups displayed a similar 2‐fold ADE (e.g., 4‐W group; 4.6 ± 0.5 for baseline vs. 10.5 ± 0.3 g/kg/day for the 1st reinstatement day) during the initial 24‐hr period. Ethanol consumption began to return to control levels 48 (7.1 ± 0.4 g/kg/day) and 72 (6.4 ± 0.4 g/kg/day) hrs later. In addition, each deprived group showed increases in the ratio of ethanol/total fluid intake upon reinstatement, and there was a tendency for sustained higher ethanol intake ratlos during the first 3 postexposure days for the 4‐, 6‐, and 8‐W grups, but only during the first 2 reinstatement days for the 2‐W group. The second deprivation did not increase the magnitude of the ADE over that observed in the first deprivation during the initial 24‐hr period of re‐exposure, but it did prolong the duration of the ADE into the 2nd and 3rd reinstatement day for the 2‐, 4‐, and 6‐W groups and into the 5th reinstatement day for the 8‐W group.Conclusions:Equivalent robust ADEs can be seen in P rats with deprivation periods of 2–8 W, which suggests that the ADE has a rapid onset and is not affected by the durations of deprivation that were tested. The duration of the ADE was prolonged in P rats exposed to a second deprivation period, suggesting that factors associated with the ADE phenomenon could be strengthened by repated deprivations.
Heritability of the Blood Pressure Response to Acute Ethanol Exposure in Five Inbred Strains of Mice
Authors: Hatton Daniel C. , Qi Yue , Belknap J. K. 
Published: May 2006

Background:Chronic alcohol consumption is a major risk factor for hypertension. There is evidence in humans that the susceptibility to alcohol‐related hypertension may vary based on genotype. As a first step in investigating the genetic basis for alcohol‐related hypertension, the current study was designed to assess the heritability of the blood pressure response to acute ethanol exposure by using AKR/J (AK), C57BL/6J (B6), DBA/2J (D2), Balb/cJ (Balb), and A/J (A) mice.Methods:Mean arterial pressure (MAP) was recorded continuously for 24 hr in freely moving mice from an indwelling femoral catheter before we tested the effects of saline or ethanol (2 g/kg ip) on blood pressure.Results:Relative to saline, ethanol caused a pressor response that peaked within 10 min, followed by a decline in MAP. Strain A mice had a significantly greater pressor response to ethanol than other strains and did not show a decline in MAP below baseline. All other strains showed a progressive fall in blood pressure below baseline across the 60 min measurement interval. Heritability was estimated to be 0.62 for the pressor response and 0.64 for the maximal depressor response. Repeated doses of ethanol at 1 hr intervals in A and B6 mice (0,2,1.5,1.5,1.5 g/kg ip) resulted in a dose‐dependent increase in MAP in A mice for the first three doses and a dose‐dependent decrease in MAP in B6 mice that was independent of blood ethanol concentrations.Conclusion:The results indicate that there is a significant genetic component to the acute blood pressure response to ethanol.
Effects of MDL 72222, a Serotonin3 Antagonist, on Operant Responding for Ethanol by Alcohol‐Preferring P Rats
Authors: McKinzie D. L. , McBride W. J. , Murphy J. M. , Lumeng L. , Li T.‐K. 
Published: May 2006

Background:Previous studies indicated that, under continuous access conditions, the 5‐HT3 antagonist MDL 72222 (MDL) effectively reduced ethanol drinking of alcohol‐preferring P rats. However, MDL was without effect when similar doses were tested under scheduled access conditions, unless the ethanol access period was randomly presented. This study examined the effects of MDL on operant responding for ethanol and water by adult male alcohol‐preferring P rats.Methods:During the dark cycle, subjects in the first experiment were trained to respond concurrently for 15% ethanol and water on a fixed‐ratio 5 (FR‐5) and FR‐1 schedule of reinforcement, respectively. Approximately 30 min before the 4‐hr operant session, rats were injected subcutaneously (sc) with saline or MDL (1,3, or 5 mg/kg). A second experiment tested the effects of 1 mg/kg MDL on operant responding for 15% ethanol in 1‐hr sessions when operant access was given at a fixed time each day (fixed scheduled access, FSA group) or at variable time periods throughout the dark cycle (variable scheduled access, VSA group).Results:In the first experiment, only the 5 mg/kg dose of MDL decreased responding for ethanol (approximately 20%) during the first 30 min of the 4‐hr session. This dose also reduced total 4‐hr responding for ethanol and water. In the second experiment, the 1 mg/kg dose of MDL had no effect on operant responding by the FSA group, but significantly reduced ethanol responding by the VSA group.Conclusions:These results suggest that 5‐HT3 receptors may be involved in mediating the reinforcing effects of ethanol, and that temporal‐environmental cues associated with the presentation of ethanol may be one factor involved in reducing the effectiveness of 5‐HT3 antagonists to attenuate ethanol intake.
Treatment of Problem Alcohol Use in Women of Childbearing Age: Results of a Brief Intervention Trial
Authors: Manwell Linda Baier , Fleming Michael F. , Mundt Marlon P. , Stauffacher Ellyn A. , Barry Kristen Lawton 
Published: May 2006

Background:Studies suggest that 14% of women age 18 to 40 drink alcohol above recommended limits. Of special concern is the increasing use of alcohol by women during pregnancy. This article reports 48 month follow‐up data from a subanalysis of a trial for early alcohol treatment (Project TrEAT) focused on women of childbearing age.Methods:Project TrEAT was conducted in the offices of 64 primary care, community‐based physicians from 10 Wisconsin counties. Of 5979 female patients ages 18 to 40 who were screened for problem drinking, 205 were randomized into an experimental group (n= 103) or control group (n= 102). The intervention consisted of two 15 min, physician‐delivered counseling visits that included advice, education, and contracting by using a scripted workbook. A total of 174 subjects (85%) completed the 48 month follow‐up procedures.Results:No significant differences were found between the experimental and control groups at baseline for alcohol use, age, socioeconomic status, smoking, depression or anxiety, conduct disorder, lifetime drug use, or health care utilization. The trial found a significant treatment effect in reducing both 7 day alcohol use (p= 0.0039) and binge drinking episodes (p= 0.0021) over the 48 month follow‐up period. Women in the experimental group who became pregnant during the follow‐up period had the most dramatic decreases in alcohol use. A logistic regression model based on a 20% or greater reduction in drinking found an odds ratio of 1.93 (confidence interval 1.07–3.46) in the sample exposed to physician intervention. Age, smoking, depression, conduct disorder, antisocial personality disorder, and illicit drug use did not reduce drinking significantly. No significant differences were found in health care utilization and health status between groups.Conclusions:This trial provides the first direct evidence that brief intervention is associated with sustained reductions in alcohol consumption by women of childbearing age. The results have enormous implications for the U.S. health care system.
Reduced Hypothalamic POMC and Anterior Pituitary CRF1 Receptor mRNA Levels After Acute, but Not Chronic, Daily “Binge”Intragastric Alcohol Administration
Authors: Zhou Yan , Franck Johan , Spangler Rudolph , Maggos Christopher E. , Ho Ann , Kreek Mary Jeanne 
Published: May 2006

Background:Endogenous corticotropin‐releasing factor (CRF), its pituitary CRF1 receptor, and proopiomelanocortin (POMC) may be involved in the hypothalamic‐pituitary‐adrenal (HPA) responses to alcohol.Methods:Alcohol (1.5 g/kg) or water was administered intragastrically to male Fischer rats after the “binge'’pattern regimen, that is, three times daily at 1 hr intervals at the beginning of the light cycle. The levels of CRF, CRF1 receptor, and POMC mRNAs in the hypothalamic‐pituitary axis were measured after acute (1 day) or chronic (14 days) binge pattern alcohol administration. Plasma levels of ACTH and corticosterone were measured to examine time‐dependent alterations of HPA responses.Results:Plasma ACTH and corticosterone levels were elevated dramatically after 1 day of acute binge pattern alcohol administration. After 14 days of chronic alcohol, however, no elevation in plasma ACTH levels and an attenuated elevation in plasma corticosterone levels were found. CRF mRNA levels in the hypothalamus were not altered after either acute or chronic alcohol administration. CRF1 receptor mRNA levels in the anterior pituitary were decreased significantly after acute administration, with no change after chronic alcohol administration. POMC mRNA levels in the anterior pituitary were not altered by either acute or chronic alcohol administration. In the hypothalamus, POMC mRNA levels were decreased significantly after acute but not chronic binge alcohol administration.Conclusions:These results suggest that (1) rats exposed to chronic binge alcohol develop tolerance in HPA activity, as shown by no elevation of ACTH and an attenuated corticosterone response to chronic alcohol after initial dramatic elevations by acute alcohol administration; (2) a concurrent acute decrease in CRF1 receptor mRNA levels in the anterior pituitary is associated with increased HPA activity, and (3) alterations of POMC gene expression in the hypothalamic region may have implications for a molecular understanding of the neuroendocrine response to alcohol.
Chronic, But Not Acute, Nicotine Exposure Attenuates Ethanol Withdrawal‐Induced Hippocampal Damage In Vitro
Authors: Prendergast Mark A. , Harris Barton R. , Mayer Sveta , Littleton John M. 
Published: May 2006

Background:Long‐term ethanol use and long‐term tobacco use frequently occur together, which suggests concurrent dependence on ethanol and nicotine. Consequences of this form of polydrug dependence are not well understood, however. Previous evidence suggests detrimental effects of long‐term ethanol and beneficial effects of nicotine exposure on neuronal viability. Thus, the present study was designed to use an organotypic hippocampal slice culture model to examine the ability of chronic and acute nicotine exposure to reduce neurotoxicity associated with withdrawal from long‐term ethanol exposure.Methods and Results:Twenty‐four hours of withdrawal after continuous 10 day ethanol exposure (50 or 100 mM in culture medium) resulted in cytotoxicity in hippocampal slice explants obtained from neonatal rat, most notably in pyramidal cell layers of the CA1 region. Exposure of slices to theN‐methyl‐d‐aspartate receptor blocker MK‐801 during ethanol withdrawal significantly reduced this toxicity. Exposure of slices to nicotine (0.1–10.0 μM) during the 24 hr withdrawal period did not reduce hippocampal damage. However, treatment of slices with nicotine (0.1–10.0 μM) during 10 days of ethanol exposure was associated with significant reductions in subsequent withdrawal‐induced cytotoxicity, an effect reduced by mecamylamine coexposure with nicotine and ethanol.Conclusions:These findings indicate the development of marked hippocampal neurotoxicity during withdrawal from long‐term ethanol exposure that is mediated, in part, by overactivation ofN‐methyl‐d‐aspartate receptors. Furthermore, these data suggest that one consequence of concurrent dependence on ethanol and nicotine may be reduced neurological damage associated with ethanol withdrawal.
Involvement of Nicotinic Receptors in Alcohol Self‐Administration
Authors: Lě A. D. , Corrigall W. A. , Watchus J. , Harding S. , Juzytsch W. , Li T.‐K. 
Published: May 2006

Background:Alcohol and nicotine, in the form of tobacco, are commonly co‐abused. Nicotinic receptors also have been implicated in alcohol action. We designed the present study to examine the possible involvement of nicotinic receptors in alcohol self‐administration.Methods and Results:Pretreatment with lower doses (0.1–0.4 mg/kg) of nicotine, administered acutely or chronically, did not affect alcohol consumption, whereas a higher dose (0.8 mg/kg) initially suppressed alcohol consumption but stimulated alcohol consumption on repeated treatment. We observed the same pattern of nicotine effects on alcohol self‐administration using an operant procedure. A dose of 0.8 mg/kg of nicotine initially suppressed operant responding for alcohol. Such suppression of alcohol self‐administration was more pronounced during the first 20 min of the 60 min operant session. Responding for alcohol in the nicotine treated group, however, was significantly increased above the saline treated group by the 5th day of treatment. Mecamylamine, a noncompetitive nicotinic receptor antagonist, reduced alcohol consumption, whereas dihydro‐β‐erythroidine (DHβE), a competitive nicotinic receptor antagonist, did not modify alcohol consumption.Conclusions:The stimulation of alcohol intake induced by nicotine treatment and the suppression of alcohol intake induced by mecamylamine provide evidence for the involvement of nicotinic receptors in alcohol consumption and/or self‐administration. The failure of DHβE to reduce alcohol consumption, however, suggests that ethanol‐nicotine interaction is mediated by other nicotinic receptor subtypes rather than α4β2 receptor subtype, or that mecamylamine acts through a nonnicotinic mechanism.
Neurocognitive Functioning of Adolescents: Effects of Protracted Alcohol Use
Authors: Brown Sandra A. , Tapert Susan F. , Granholm Eric , Delis Dean C. 
Published: May 2006

Background:The present study examined associations between alcohol involvement in early to middle adolescence and neuropsychological (NP) functioning.Methods:Alcohol‐dependent adolescents (n= 33) with over 100 lifetime alcohol episodes and without dependence on other substances were recruited from alcohol/drug abuse treatment facilities. Comparison (n= 24) adolescents had no histories of alcohol or drug problems and were matched to alcohol‐dependent participants on age (15 to 16 years), gender, socioeconomic status, education, and family history of alcohol dependence. NP tests and psychosocial measures were administered to alcohol‐dependent participants following 3 weeks of detoxification.Results:Alcohol‐dependent and comparison adolescents demonstrated significant differences on several NP scores. Protracted alcohol use was associated with poorer performance on verbal and nonverbal retention in the context of intact learning and recognition discriminability. Recent alcohol withdrawal among adolescents was associated with poor visuospatial functioning, whereas lifetime alcohol withdrawal was associated with poorer retrieval of verbal and nonverbal information.Conclusions:Deficits in retrieval of verbal and nonverbal information and in visuospatial functioning were evident in youths with histories of heavy drinking during early and middle adolescence.
Evidence of a Structural Effect for Alcohol Outlet Density: A Multilevel Analysis
Authors: Scribner Richard A. , Cohen Deborah A. , Fisher William 
Published: May 2006

Background:Ecological studies reveal that alcohol‐related outcomes tend to occur in high alcohol outlet density neighborhoods. The ecological design of these studies limits the interpretation of the findings in terms of the level of the effect. The effect of alcohol outlet density could be related to greater individual access to alcohol, an individual level effect, or to the grouping of drinkers by neighborhood, a structural effect at the neighborhood level.Methods:To differentiate between individual and neighborhood level possibilities, we conducted a multilevel study. Individual distance to the closest alcohol outlet was the individual level measure of the effect of alcohol outlet density, whereas the mean distance to the closest alcohol outlet for all individuals within a census tract was the neighborhood level measure for the effect of alcohol outlet density. We analyzed telephone surveys of 2604 telephone households within 24 census tracts stratified by poverty status and alcohol outlet density. Individual distance to alcohol outlets, age, sex, race/ethnicity, and level of education were entered as individual level covariates, and their corresponding aggregated means were entered as census tract level covariates (i.e., mean distance to outlets, mean age, percentage male, percentage Black, mean education).Results:Analysis of variance revealed that 16.2% of the variance in drinking norms and 11.5% of the variance in alcohol consumption were accounted for at the census tract level. In multivariate hierarchical analysis, individual distance to the closest alcohol outlet was unrelated with drinking norms and alcohol consumption, whereas mean distance to the closest alcohol outlet demonstrated a negative relation with drinking norms (βc= ‐5.50 ± 2.37) and with alcohol consumption (βe= ‐0.477 ± 0.195); that is, the higher the mean distance to the closest alcohol outlet, the lower the mean drinking norms score and mean level of alcohol consumption.Conclusions:The findings suggest that the effect of alcohol outlet density on alcohol‐related outcomes functions through an effect at the neighborhood level rather than at the individual level. Problem drinkers tend to be grouped in neighborhoods, an effect predicted by alcohol outlet density.