bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex Differences in the Influence of COMT Val158Met on Alcoholism and Smoking in Plains American Indians
Authors: Enoch Mary‐Anne , Waheed Juwaria F. , Harris Claudia R. , Albaugh Bernard , Goldman David 
Published: February 2006

Background: Alcoholism and heavy smoking are highly comorbid and are cotransmitted in the general U.S. population; however little is known about comorbidity in American Indians. The catechol‐O‐methyltransferase (COMT) functional polymorphism, Val158Met, has been associated with alcoholism in Caucasians. The aims of our study were firstly to investigate patterns of alcohol and tobacco consumption and comorbidity between alcoholism and smoking in Plains American Indians and secondly to determine the influence, including sexual dimorphic effects, of COMT Val158Met and COMT haplotypes, on these behaviors.Methods: Diagnostic and Statistical Manual‐III‐R lifetime diagnoses were assigned to 342 community‐ascertained Plains American Indians (201 women, 141 men). Lifetime drinking and smoking histories were obtained. Five COMT loci, including Val158Met, were genotyped. Haplotype‐based analyses identified 1 block with 3 common haplotypes; 2 included Val158, and 1 had the Met158 allele.Results: The alcoholics drank heavily (12±8 drinks/drinking day) but episodically (max 10±8 d/mo). Although 62% of male alcoholics and 40% of female alcoholics were smokers (≥10 cigarettes/d), only 12% of alcoholic men and 8% of alcoholic women smoked heavily (>20/d). In women, the COMT Val158 allele frequency was maximal in alcoholic smokers (0.85), decreasing to 0.74 in nonalcoholic smokers, 0.67 in alcoholic nonsmokers, and 0.64 in nonalcoholic nonsmokers (χ2=11.1, 3 df, p=0.011). Women showed a main effect of Val158 on smoking (p=0.003). Both male and female alcoholics were more likely to have at least 1 Val158 allele compared with nonalcoholics (0.95 vs 0.88, p<0.05). Approximately 30% of all participants were long‐term, nonaddicted light, social smokers (3.6±1.7 cigarettes/d); they had the same Val158Met frequencies as nonsmokers. Haplotype analyses supported the Val158Met findings; however, only 1 of the 2 Val158 haplotypes was implicated.Conclusions: Plains Indians have different smoking and drinking patterns and considerably less comorbidity between alcoholism and heavy smoking compared with the general U.S. population. Our COMT Val158Met results suggest that there may be both sex differences in the genetic origins of alcoholism and smoking in this population and overlap in genetic vulnerability to both addictions in women.
Reestablishing an Intragastric Ethanol Self‐infusion Model in Rats
Authors: Fidler Tara L. , Clews Tara W. , Cunningham Christopher L. 
Published: February 2006

Background: There is a scarcity of behavioral models that will reliably produce ethanol intakes in rodents at levels that induce or maintain dependence. The present experiments were designed to reestablish a model that uses passive intragastric (IG) infusion of ethanol to induce tolerance/dependence/withdrawal before allowing rats to self‐infuse ethanol intragastrically.Methods: Sprague–Dawley rats were surgically implanted with IG catheters and allowed to recover. During the passive infusion phase (3–6 days), rats in the experimental group were passively infused with 10% (v/v) ethanol (3.3–12.2 g/kg/d). Rats in the control group were not infused. During the self‐infusion phase (5–6 days), all rats had access to 2 flavored solutions. Licks on 1 solution were paired with ethanol infusions (20%, v/v) whereas licks on the other solution were unpaired. Experiments differed in the specific passive infusion parameters and in the ethanol intake limit during self‐infusion.Results: Rats in the experimental groups self‐infused more ethanol per day (means of 4–7 g/kg/d) than did rats in the control group (means of 0–2.6 g/kg/d). Across all 3 studies, individual total daily intakes exceeded 5 g/kg on 35% of the self‐infusion days in ethanol‐preexposed rats compared with <1% of the self‐infusion days in the control rats. Ethanol‐exposed rats also infused a substantially higher percentage (42%) of their total ethanol intake in relatively large bouts (>1.5 g/kg) compared with control rats (<10%). The addition of a daily 6‐hour ethanol‐free period during the passive infusion phase (in Experiments 2 and 3) led to higher ethanol intakes than in Experiment 1. Results of a control experiment showed that differences between experimental and control groups in Experiments 1 to 3 were a result of ethanol experience and not a general effect of differential infusion experience.Conclusions: Relatively short periods of passive IG infusion of ethanol induced levels of ethanol self‐infusion in genetically heterogeneous rats that were comparable with drinking intakes previously reported in rats selectively bred for ethanol intake/preference. Although the induction of dependence/withdrawal may have played a role in this outcome, an alternative interpretation is that experimental rats self‐infused more ethanol because passive exposure produced tolerance to aversive pharmacological effects that would otherwise limit intake of the paired flavor because of development of conditioned taste aversion. The current findings provide a strong basis for future work designed to identify parametric determinants of this form of self‐administration, its sensitivity to genetic influences, and its neurobiological substrates.
Delay Discounting Predicts Behavioral Sensitization to Ethanol in Outbred WSC Mice
Authors: Mitchell Suzanne H. , Reeves Jamie M. , Li Na , Phillips Tamara J. 
Published: February 2006

Background: Alcoholic individuals discount the value of future rewards more steeply than social drinkers, which is viewed as symptomatic of higher levels of impulsivity. However, the mechanisms underlying this difference are unknown. This study examined 2 hypotheses about the relationship between discounting and ethanol's effects in mice: (1) steep discounters are less sensitive to the initial stimulant‐like effects of ethanol and (2) steep discounters exhibit greater behavioral adaptation to stimulant effects with repeated ethanol exposure.Methods: An adjusting amount procedure was used to assess discounting as a function of delay in ethanol‐naïve genetically heterogeneous WSC mice. Mice chose between a small amount of sucrose solution delivered immediately and 19.5 μL delivered following a delay (0, 2, 4, 8, or 12 seconds, varied between sessions). Within sessions, the amount (μL) of immediate sucrose was adjusted until animals became indifferent between the immediate and specific delayed reward. Hyperbolic discount functions were fitted to quantify the degree of delay discounting. Then, in a within‐subjects design over 13 days, mice received a pattern of daily injections of saline or ethanol, and after certain treatments their locomotor activity was assessed for 15 minutes.Results: Animals with steeper discount functions (greater impulsivity) tended to exhibit less locomotor stimulation on their initial exposure to ethanol. However, steeper discounting was positively associated with increases in locomotor activity after repeated exposure (sensitization), indicating that steep discounters showed higher levels of sensitization to the stimulating effects of ethanol.Conclusions: These results suggest 2 behavioral effects of ethanol, associated with an increased risk for alcohol abuse, that are associated with variations in delay discounting.
Differential Effects of Alcohol Consumption and Withdrawal on Circadian Temperature and Activity Rhythms in Sprague–Dawley, Lewis, and Fischer Male and Female Rats
Authors: Taylor Anna N. , Tio Delia L. , Bando Jennifer K. , Romeo Horacio E. , Prolo Paolo 
Published: February 2006

Background: Hypothalamic synthesis and secretion of corticotropin‐releasing hormone (CRH), a putative mediator of various behavioral and physiological responses to ethanol (EtOH), is defective in inbred Lewis (LEW) rats in comparison with their genetically related inbred Fischer 344 (F344) and outbred Sprague–Dawley (S–D) strains. We aimed to characterize the effects of continuous EtOH consumption and withdrawal on circadian patterns of body temperature and spontaneous locomotor activity in males and females of these 3 strains.Methods: Adult LEW, F344, and S–D males and randomly cycling females were fed an EtOH‐containing liquid diet or the control (pair‐fed or lab chow and water) diet for 14 days. Biotelemetric body temperature data for the last 3 days of EtOH diet feeding and the first 3 days of withdrawal were subjected to cosinor analysis of the circadian rhythm parameters of midline‐estimating statistic of rhythm (MESOR), amplitude, and acrophase. Mean dark‐phase activity during these periods was also computed.Results: In the control diet condition, the MESORs and amplitudes of LEW males were lower than those of F344 males. MESORs of rhythms of LEW females were lower than those of both F344 and S–D females. Ethanol consumption caused hypothermia with reduced MESORs and amplitudes of LEW and F344 males and amplitudes of F344 and S–D females. Upon withdrawal, MESORs of the males increased during each day as the amplitudes decreased, reflective of their initial withdrawal‐induced dark‐phase hypothermia, which was most pronounced in the LEW males, followed by light‐phase hyperthermia. MESORs of females were not affected by withdrawal; their amplitudes were differentially affected. Acrophase of LEW males shifted from dark to light on the first day of withdrawal. All rats responded to EtOH exposure with a reduction of dark‐phase spontaneous locomotor activity and an immediate increase upon withdrawal.Conclusions: Body temperature rhythms of the males were generally more affected by EtOH consumption and withdrawal than the females; within each sex, LEW and F344 rats differed significantly. The specific hormonal factors that mediate the differential temperature responses remain to be defined.
Early Ethanol's Anxiolytic Effects Assessed Through an Unconditional Stimulus Revaluation Procedure
Authors: Pautassi Ricardo Marcos , Sanders Sarah , Miller Stacie , Spear Norman , Molina Juan Carlos 
Published: February 2006

Background: Even though ethanol is considered to exert antianxiety effects, the existence of such properties during early ontogeny of the rat has rarely received attention, mainly because of the restricted behavioral repertoire of the pup. This study evaluated ethanol's anxiolytic properties in preweanling rats through an unconditional stimulus revaluation procedure.Methods: Optimal parameters for the acquisition of an odor avoidance response were obtained in Experiment 1. In Experiment 2 preweanlings experienced 4 conditioning trials defined by a 5 minute exposure to a lemon odor while they were intraorally infused with a sapid aversive stimulus (citric acid). Twenty‐four hours later, pups were briefly exposed to the acid 5 minutes after being administered with 0.0, 0.25, 0.5, 1.25, or 2.5 g/kg of ethanol. Odor preferences were then evaluated in a 2‐way odor preference test. Blood ethanol concentrations (BEC's) derived from these doses were assessed in Experiment 3. In Experiment 4, citric acid mediated‐conditioning was followed by a similar odor‐preference test after pups were re‐exposed to the acid either 5 or 25 minutes after receiving a 2.5 g/kg ethanol dose. Ethanol's effects upon the avoidance response were also analyzed in an alternative rat strain (Experiment 5).Results: Moderate to low ethanol doses ameliorated the otherwise strong avoidance response. Further experiments: (a) replicated these phenomena, (b) established that they are correlated with BEC's in the range of 17–70 mg%, and (c) Indicated that ethanol's influence upon an avoidance response changes as a function of the temporal course of the intoxication.Conclusions: Acute ethanol interacts with aversive nondrug‐mediated learning. These findings are likely to be discussed in terms of possible negative reinforcing properties of ethanol and indicate that this drug exerts differential motivational effects during the course of the intoxication. The devaluation procedure should be considered as an alternative method to assess ethanol's motivational properties.
Serum Lipids and Risk Factors for Attempted Suicide in Patients with Alcohol Dependence
Authors: Deisenhammer Eberhard A. , Lechner‐Schoner Theresia , Kemmler Georg , Ober Alexander , Braidt Eva , Hinterhuber Hartmann 
Published: February 2006

Background: Alcohol dependence is a major risk factor for suicidal behavior. Although a number of risk factors have been suggested there is still no well‐defined risk profile for attempted suicide in alcoholic patients. Alterations of serum lipids have been associated with completed as well as attempted suicide and with suicidal ideation. This study investigated potential demographic and clinical risk factors for attempted suicide in alcohol‐dependent patients taking serum lipids additionally into consideration.Methods: One‐hundred ten alcohol‐dependent patients who were admitted to a psychiatric university hospital department for inpatient treatment were grouped according to whether or not they had a lifetime history of attempted suicide. Attempters versus nonattempters as well as attempters who used a violent versus a nonviolent suicide method were compared.Results: Patients who had attempted suicide at least once in their life differed significantly from those who had no history of suicide attempts. Univariate analyses showed that they were younger (41.7 years vs 46.8 years; p=0.003), were more often smokers (97% vs 77%; p=0.011), had more frequently coabused benzodiazepines (54% vs 17%; p=0.002), and scored currently higher on the Montgomery and Åsberg Depression Rating Scale (MADRS) global scale (26.3 vs 20.2; p=0.005) as well as the “suicidal thoughts” item (1.8 vs 0.6; p=0.001). Additionally, they had higher serum triglyceride levels (178.9 vs 127.5; p=0.039). A logistic regression analysis left coabuse of benzodiazepines [odds ratio (OR), 5.26; p=0.001], younger age (OR per year increase of age, 0.91; p=0.006), and current MADRS item 10 (“suicidal thoughts”) score (OR per point increase in MADRS item 10 score, 1.43; p=0.019) as significant factors. Suicide attempters who had used a violent method were significantly more often male (82% vs 44%; p=0.035), were younger (38.2% vs 45.1 years; p=0.008), and had less frequently coabused tranquilizers (35% vs 78%; p=0.018) than nonviolent attempters.Conclusions: These findings contribute to the development of a more specific profile of alcohol‐dependent individuals at risk for suicidal behavior. Further research is required to determine the role of serum triglycerides for suicidal behavior in patients with alcohol dependence.
Effects of the History of Conduct Disorder on the Iowa Gambling Tasks
Authors: Kim Yang Tae , Lee Seung Jae , Kim Sang Heon 
Published: February 2006

Background: Recent research conducted with the Iowa Gambling Task (GT) suggests decision‐making impairments in substance dependence, as well as behavior disorders such as conduct disorder and attention‐deficit/hyperactivity disorder. However, little is known about the past history of conduct disorder on decision making.The purpose of this study was to test the possible effect of past history of conduct disorder on GT performance and how this factor could contribute to the performance on GT in alcohol‐dependent patients.Methods: Four subject groups were tested: (1) alcohol‐dependent patients with (n=28) and (2) alcohol‐dependent patients without (n=28), a history of conduct disorder and (3) normal controls with (n=10) and (4) normal controls without (n=30) a history of conduct disorder. Demographic and alcohol‐related variables were evaluated, and a decision‐making task, “Iowa GT,” both original and variant version, were applied.Results: As a whole, normal controls with a history of conduct disorder and alcohol‐dependent patients with or without a history of conduct disorder show impaired decision making because of hypersensitivity to reward and hyposensitivity to punishment. However, no significant differences were noted between alcohol‐dependent patients either with or without a history of conduct disorder on gambling performance.Conclusions: These results indicate that the history of conduct disorder may contribute to impaired decision making on GT. Furthermore, this kind of decision‐making pattern may represent one of common underlying mechanisms in both conduct disorder and alcohol dependence.
Single‐ and Multiple‐Dose Pharmacokinetics of Long‐acting Injectable Naltrexone
Authors: Dunbar Joi L. , Turncliff Ryan Z. , Dong Qunming , Silverman Bernard L. , Ehrich Elliot W. , Lasseter Kenneth C. 
Published: February 2006

Background: Oral naltrexone is effective in the treatment of alcohol dependence; however, a major limitation of its clinical utility is poor patient adherence to the daily dosing schedule. A biodegradable, long‐acting naltrexone microsphere formulation was developed to achieve continuous naltrexone exposure for 1 month in the treatment of alcohol dependence.Methods: The single‐ and multiple‐dose safety and pharmacokinetics of a long‐acting naltrexone microsphere preparation were evaluated in healthy subjects. One group of subjects (n=28) received a single dose of oral naltrexone 50 mg followed by a single gluteal intramuscular (IM) injection of long‐acting naltrexone 190 or 380 mg or placebo. A different group of subjects (n=14) received oral naltrexone 50 mg daily for 5 days, followed by IM long‐acting naltrexone 380 mg or placebo every 28 days for a total of 4 doses. A 7‐day washout period separated oral and IM administrations. Blood samples were collected to determine plasma concentrations of naltrexone and the primary metabolite, 6β‐naltrexol.Results: After a single IM injection of long‐acting naltrexone 380 mg, naltrexone plasma concentrations were measurable in all subjects for at least 31 days postdose. The pharmacokinetics were proportional to the dose and multiple dose observations were consistent with single dose observations. Mean apparent elimination half‐lives for naltrexone and 6β‐naltrexol ranged from 5 to 7 days. Exposure to 6β‐naltrexol was reduced with IM injection compared with that oral administration. No serious adverse events occurred.Conclusions: This study demonstrated that the long‐acting naltrexone formulation was well tolerated, displayed predictable pharmacokinetics, and resulted in no meaningful drug accumulation upon multiple dosing. Intramuscular administration avoids first‐pass metabolism and changes the exposure ratio of 6β‐naltrexol to naltrexone compared with oral administration. By providing continuous exposure to naltrexone for several weeks following IM injection, this long‐acting naltrexone formulation may offer therapeutic benefit to those patients who experience difficulty adhering to the daily administration schedule necessitated by oral naltrexone therapy.
Esophageal Squamous Cell Carcinoma and Aldehyde Dehydrogenase‐2 Genotypes in Japanese Females
Authors: Yokoyama Akira , Kato Hoichi , Yokoyama Tetsuji , Igaki Hiroyasu , Tsujinaka Toshimasa , Muto Manabu , Omori Tai , Kumagai Yoshiya , Yokoyama Masako , Watanabe Hiroshi 
Published: February 2006

Background: Aldehyde dehydrogenase‐2 (ALDH2) is the key enzyme for elimination of acetaldehyde, an established animal carcinogen produced after drinking. In persons with inactive ALDH2, the body fails to metabolize acetaldehyde rapidly, leading to excessive accumulation of acetaldehyde. Inactive heterozygous ALDH2 enhances the risk of esophageal squamous cell carcinoma (SCC) in Japanese male drinkers.Methods: We studied whether this is the case for women. The risk factors of esophageal SCC were examined in 52 Japanese women with esophageal SCC and 412 cancer‐free Japanese women.Results: The increasing trend in cancer risk according to the quantity of alcohol consumption was significantly steeper in women with inactive heterozygous ALDH2 than in those with active ALDH2 [adjusted odds ratios (ORs) (95% confidence intervals (CIs)) per +7 U/wk increment of alcohol drinking were 3.91 (2.09–7.31) and 1.39 (0.92–2.09), respectively; p=0.006 for difference in OR; 1 Ut=22 g of ethanol]. The results obtained using an alcohol‐flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping [adjusted ORs (95% CIs) per +7 U/wk increment of alcohol drinking were 3.94 (1.87–8.31) and 1.46 (0.96–2.23) in those with and without flushing, respectively; p=0.021 for difference in OR]. The risk of esophageal cancer was markedly higher in heavy drinkers with ALDH2*1/*2 than in never/rare drinkers with ALDH2*1/*1 [adjusted OR (95% CI)=59.1 (4.65–750)]. Other independent significant risk factors of esophageal SCC were smoking, a preference for hot food or drinks, and lower intake of green and yellow vegetables.Conclusions: Japanese men and women shared several common risk factors of esophageal SCC, including drinking with inactive heterozygous ALDH2.
Alcohol Consumption Before and During Pregnancy Comparing Concurrent and Retrospective Reports
Authors: Alvik Astrid , Haldorsen Tor , Groholt Berit , Lindemann Rolf 
Published: February 2006

Background: Reported alcohol consumption during pregnancy has proven to be higher when reported retrospectively during or after the pregnancy, compared with concurrent reports. In a longitudinal, population‐based questionnaire study, we investigated whether these findings could be replicated.Methods: A longitudinal, population‐based questionnaire study. Among a representative half of pregnant women in Oslo, 92% accepted to join the study. Non‐Norwegian speaking and/or immigrants from nonwestern countries were not invited. Questionnaires were answered at 17 (T1) and 30 weeks of pregnancy (T2) and 6 months after term (T3). The response rate was at T1 93% (N= 1,749), at T2 82%, and at T3 94% [representing 86% (T1), 70% (T2), and 64% of those invited to join the study].Results: Significantly more alcohol consumption after pregnancy recognition was reported retrospectively at both T2 and T3 [T2 0.15 and T3 0.18 standard units per week (SU/wk)] than concurrently at T1 or T2 (T1 0.10 and T2 0.14 SU/wk). When comparing the 2 retrospective reports at T2 and T3, there was a significant increase over time. Predictive factors for higher retrospective reports were higher age, more SU per week before pregnancy, reported alcohol use after pregnancy recognition (at T1), and depression after the pregnancy. A predictive factor for lower retrospective reporting was anxiety during, but not after, the pregnancy. Contrary to previous suggestions, anxiety concerning abnormality in the 6‐month‐old child was not a predictive factor.Conclusion: Concurrently reported alcohol consumption during pregnancy is probably under‐reported. Thus, concurrent reports appear to underestimate fetal exposure.