2024-03-29T15:40:14Zhttp://open-archive.highwire.org/handler
oai:open-archive.highwire.org:alcalc:37/5/4092015-05-19HighWireOUPalcalc:37:5
CARDIOPROTECTIVE EFFECTS OF LIGHT-MODERATE CONSUMPTION OF ALCOHOL: A REVIEW OF PUTATIVE MECHANISMS
Agarwal, Dharam P.
REVIEWS
— There is abundant epidemiological and clinical evidence showing that light–moderate drinking is associated with a reduced risk of coronary heart disease (CHD), total and ischaemic stroke and total mortality in middle-aged and elderly men and women. The epidemiological evidence suggests a J- or U-shaped relationship between alcohol and CHD. However, the apparent benefits of moderate drinking on CHD mortality are offset at higher drinking levels by increasing risk of death from other types of heart diseases (cardiomyopathy, arrhythmia etc.), neurological disorders, cancer, liver cirrhosis, and traffic accidents. The plausible mechanisms for the putative cardioprotective effects include increased levels of high-density lipoprotein cholesterol, decreased levels of low-density lipoprotein cholesterol, prevention of clot formation, reduction in platelet aggregation, and lowering of plasma apolipoprotein(a) concentration. Thus, alcohol reduces the risk of coronary vascular diseases both by inhibiting the formation of atheroma and decreasing the rate of blood coagulation.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/409
http://dx.doi.org/10.1093/alcalc/37.5.409
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4162015-05-19HighWireOUPalcalc:37:5
A NICE TRY THAT FAILS: THE SWEDISH COUNCIL ON TECHNOLOGY ASSESSMENT IN HEALTH CARE (SBU) EVALUATION OF THE EFFECT OF TREATMENT OF ALCOHOL AND DRUG PROBLEMS: THE EPIDEMIOLOGIST'S VIEW
Poikolainen, Kari
INVITED COMMENTARIES
— <b>Background and Aims:</b> The Swedish Council on Technology Assessment in Health Care (SBU) has recently published a large, >800-page systematic review. It reviews brief interventions to reduce alcohol intake, long-term prognosis of substance dependence, obstetric questions and economic aspects of addiction treatments. The main part aims to evaluate treatments on alcohol and other addictive substances by meta-analytical techniques. <b>Results and Conclusions:</b> The report summarizes 641 individual studies. Unfortunately, several methods are weak, some inadequately documented, and many conclusions rest on shaky grounds.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/416
http://dx.doi.org/10.1093/alcalc/37.5.416
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4192015-05-19HighWireOUPalcalc:37:5
THE SWEDISH STATE HEALTH TECHNOLOGY BOARD (SBU) REPORT ON TREATMENT OF ALCOHOL AND DRUG MISUSE: AN ECONOMIST'S VIEW
Brooks, Richard
INVITED COMMENTARIES
— The Swedish State Health Technology Board (SBU) has published a Report on the treatment of alcohol and drug misuse (<cross-ref refid="SBU-2001" type="bib">SBU, 2001</cross-ref>). This article is a brief Commentary on the economic issues raised in Chapter 9 of the Report, in particular, the question of ‘how cost-effective are the different treatment alternatives?’ An outline is given of how the authors approached the economic work, with particular reference to a standard checklist approach to judging the quality of published economic appraisals. A paucity of such appraisals was retrieved and detailed review of just 16 papers was undertaken. The authors are critical of the lack of quality of economic work in the substance misuse area and their main points are summarized here. The main conclusion drawn is that no economic judgements can be made about alternative treatment approaches, and more study and research are needed in this area. Chapter 9 is, on balance, a good attempt at a critical review of the economic appraisal literature. Unfortunately the main Report provides a series of summary judgements on the effectiveness or otherwise of alternative treatments, which, while recognizing the need for further cost-effectiveness work, essentially ignores the conclusion drawn in the economics chapter. This is likely to do a disservice to the cause of appropriate resource allocation in the substance misuse area.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/419
http://dx.doi.org/10.1093/alcalc/37.5.419
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4212015-05-19HighWireOUPalcalc:37:5
INTERMITTENT ETHANOL EXPOSURE INCREASES THE NUMBER OF CEREBELLAR MICROGLIA
Riikonen, Jarno
Jaatinen, Pia
Rintala, Jyrki
Pörsti, Ilkka
Karjala, Kirsi
Hervonen, Antti
Experimental Studies
— <b>Aims:</b> The number of cerebellar microglia after 51/2 months of continuous or intermittent ethanol exposure was studied using the optical dissector method. <b>Methods:</b> Male Wistar rats were divided into three groups: an intermittently ethanol-exposed group, a continuously ethanol-exposed group and a control group (<it>n</it> = 6 in each group). The intermittently treated rats had two ethanol-withdrawal periods per week throughout the experiment. The number of microglia was measured in the anterior (folium II) and the posterior (folium X) cerebellar vermis. Tomato (<it>Lycopersicon esculentum</it>) lectin was used to stain the cerebellar microglia. <b>Results:</b> The volumes of folia II and X were similar in all the groups. The number of microglia increased in the molecular layer of folium II in the intermittently ethanol-exposed group compared with the continuously exposed and control groups. In the granular layer, there were no differences between the groups in the number of microglia. <b>Conclusions:</b> The results suggest that the number of cerebellar microglia increases in the anterior vermis before any ethanol-induced cerebellar atrophy is discernible. Repeated ethanol withdrawals seem to be more essential in inducing microgliosis than ethanol intoxication <it>per se</it>.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/421
http://dx.doi.org/10.1093/alcalc/37.5.421
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4272015-05-19HighWireOUPalcalc:37:5
CONDITIONED TASTE AVERSION AND THE MYERS' HIGH-ETHANOL-PREFERRING RAT
Lucas, Lou Anne C.
McMillen, Brian A.
Experimental Studies
— <b>Aims:</b> Male and female Myers’ high-ethanol-preferring (mHEP) rats were compared to outbred controls in a taste aversion paradigm. <b>Methods:</b> Alcohol-naïve rats were adapted to a 2-h access to water. Each rat was given either 0.05% saccharin (w/v) or 7% ethanol (v/v) as a novel solution for 1 h, after which either 0.5 M LiCl, as the aversive stimulus, or NaCl, as the control, was injected intraperitoneally. Each rat was tested 48 h later by presentation of the same solution. <b>Results:</b> After LiCl injections, saccharin consumption declined 21.6% in female Sprague–Dawley, 9.5% in female mHEP, 33.3% in male Wistar, and 38.3% in male mHEP rats. Ethanol consumption in these groups declined by 88.5, 30, 45 and 52%, respectively. These mHEP rats were then screened for 24-h alcohol consumption on a 10-day 3–30% ethanol vs water ‘step-up’ procedure. During the step-up procedure, only the male mHEP rats trained with ethanol for taste aversion drank less ethanol at the 3–5% concentrations than did rats trained with saccharin. The female mHEP rats did not learn an aversion to either saccharin or ethanol. <b>Conclusions:</b> The female mHEP rat consumes copious amounts of ethanol, but the basis for this consumption may be different from that of the male mHEP rat.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/427
http://dx.doi.org/10.1093/alcalc/37.5.427
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4322015-05-19HighWireOUPalcalc:37:5
EFFECTS OF ACETALDEHYDE ON c-fos mRNA INDUCTION IN THE PARAVENTRICULAR NUCLEUS FOLLOWING ETHANOL ADMINISTRATION
Kinoshita, Hiroshi
Jessop, David S.
Roberts, David J.
Ameno, Kiyoshi
Ijiri, Iwao
Hishida, Shigeru
Harbuz, Michael S.
Experimental Studies
— <b>Aims:</b> The effect of acetaldehyde on c-fos mRNA expression in the paraventricular nucleus (PVN) of the rat was examined using <it>in situ</it> hybridization histochemistry. <b>Methods:</b> Increases in acetaldehyde concentrations were induced using cyanamide (a potent inhibitor of aldehyde dehydrogenase), in the presence of two different doses of ethanol. Concentrations of blood ethanol and acetaldehyde were determined by head space gas chromatography. <b>Results:</b> Neither cyanamide alone nor the low dose of ethanol (1 g/kg) alone increased c-fos expression in the PVN. However, the combination of cyanamide and low dose ethanol resulted in a significant and maximal increase in c-fos mRNA in the PVN. High dose ethanol (3 g/kg) resulted in a significant increase in c-fos mRNA. This stimulation also appeared maximal as there was no further increase in c-fos expression in the presence of cyanamide. <b>Conclusions:</b> These data suggest that acetaldehyde accumulation in blood has an important stimulatory effect on c-fos expression in the PVN at low ethanol concentrations. Furthermore, this stimulation of c-fos mRNA appears to be an either/or response: not activated in response to low dose ethanol, but maximally to high dose ethanol. These data also provide further evidence for a dissociation between the activation of c-fos and corticotrophin-releasing factor (CRF) mRNA in the PVN, as we have previously demonstrated that this dose of cyanamide alone is sufficient to evoke a sustained increase in plasma corticosterone and an increase in CRF mRNA.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/432
http://dx.doi.org/10.1093/alcalc/37.5.432
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4362015-05-19HighWireOUPalcalc:37:5
SUCROSE SELF-ADMINISTRATION PREDICTS ONLY INITIAL PHASE OF ETHANOL-REINFORCED BEHAVIOUR IN WISTAR RATS
Rogowski, Artur
Kostowski, Wojciech
Bienkowski, Przemyslaw
Experimental Studies
— <b>Aims:</b> To characterize the relationship between the sucrose- and ethanol-reinforced behaviour in Wistar rats. <b>Methods:</b> Subjects (<it>n</it> = 31) were trained to lever press for 8% (v/v) ethanol in an operant procedure where increasing concentrations of ethanol were introduced in the presence of 8% (w/v) sucrose. The sucrose concentration was subsequently decreased from 8 to 0%. Subjects were allowed to stabilize their intake of 8% ethanol over the next 20 days. <b>Results:</b> Self-administration of 8% sucrose (ml/kg) significantly correlated with ethanol consumption (g/kg) on days 1–5 of the 8% ethanol self-administration period. This relationship completely disappeared during the subsequent weeks of ethanol self-administration (days 6–20). <b>Conclusions:</b> The results of the present study, combined with our previous findings, may indicate that self-administration of sucrose predicts only the initial phase of ethanol-taking behaviour in Wistar rats.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/436
http://dx.doi.org/10.1093/alcalc/37.5.436
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4412015-05-19HighWireOUPalcalc:37:5
CHANGES IN P300 LATENCY DURING THE EARLY WITHDRAWAL PERIOD IN CHRONIC ALCOHOL-DEPENDENT PATIENTS: TWO CASE REPORTS
Sekine, Atsushi
Niiyama, Yoshitsugu
Abe, Masato
Shimizu, Tetsuo
Human Studies
— <b>Aims:</b> The present study focused on changes in P300 of the event-related potential (ERP) in two patients with alcohol dependence recorded throughout their alcohol withdrawal period. <b>Results:</b> As a result of this investigation, the peak latency of P300 in each patient was significantly shorter 2 or 3 days after abstinence from alcohol, when marked neurological manifestations appeared, compared to that of the control obtained from 8 to 10 days after cessation of drinking. <b>Conclusions:</b> It seems reasonable to conclude that the shortening of P300 latency reflects the enhancement of brain activity during the early withdrawal period and that an investigation of changes in P300 would be helpful to clarify the nature of neural activity in the brain associated with alcohol withdrawal.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/441
http://dx.doi.org/10.1093/alcalc/37.5.441
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4442015-05-19HighWireOUPalcalc:37:5
A COMPARISON OF ALCOHOL SCREENING INSTRUMENTS AMONG UNDER-AGED DRINKERS TREATED IN EMERGENCY DEPARTMENTS
Kelly, Thomas M.
Donovan, John E.
Kinnane, Janet M.
Taylor, David M. C. D.
Human Studies
— <b>Aims:</b> Few studies have examined the adequacy of adult-validated alcohol screening measures when used with adolescents and young adults. A total of 103 subjects (55 males, 48 females) participated in a study of alcohol use among under-aged drinkers conducted in two emergency departments. <b>Methods:</b> Participants completed three brief screening instruments for problematic alcohol use: the Alcohol Use Disorders Identification Test (AUDIT); a modified version of the TWEAK; and the CAGE. <b>Results and Conclusions:</b> Missing data on the TWEAK, lower internal consistency for the TWEAK and CAGE, and the better ability of the AUDIT to differentiate problem drinkers from non-problem drinkers, suggest that the AUDIT performs best in screening for problematic alcohol use among under-aged drinkers treated in emergency departments.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/444
http://dx.doi.org/10.1093/alcalc/37.5.444
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4512015-05-19HighWireOUPalcalc:37:5
HARMFUL DRINKING IN MILITARY VETERANS WITH POST-TRAUMATIC STRESS DISORDER: ASSOCIATION WITH THE D2 DOPAMINE RECEPTOR A1 ALLELE
Young, R. McD.
Lawford, B. R.
Noble, E. P.
Kann, B.
Wilkie, A.
Ritchie, T.
Arnold, L.
Shadforth, S.
Human Studies
— <b>Aims:</b> The frequency of the Taq I A alleles (A1 and A2) of the D2 dopamine receptor (DRD2) gene was examined in Caucasian post-traumatic stress disorder (PTSD) patients and controls. <b>Results:</b> In 91 PTSD patients, the frequency of the A1 allele was higher (<it>P</it> = 6.12 × 10−3) than in the 51 controls. In the 38 PTSD harmful drinkers (≥60 g alcohol/day), A1 allelic frequency was higher (<it>P</it> = 3.91 × 10−2) than in the 53 non-harmful drinkers (<60 g alcohol/day), the former being also higher (<it>P</it> = 3.76 × 10−4) than in controls. However, there was no difference between non-harmful drinkers and controls. Based on DRD2 allelic association, the 35 PTSD patients with the A1+ (A1A1, A1A2) allele consumed more than twice the daily amount of alcohol than the 56 patients with the A1− (A2A2) allele (<it>P</it> = 1.94 × 10−3). When the hourly rate of alcohol consumed was compared, A1+ allelic patients consumed twice the rate of the A1− allelic patients (<it>P</it> < 10−7). <b>Conclusion:</b> The DRD2 A1 allele was associated with PTSD. However, this association was found only in the harmful drinkers. PTSD patients with the A1+ allele consumed more alcohol than patients with the A1− allele. The importance of determining alcohol consumption in DRD2 association studies with PTSD is suggested.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/451
http://dx.doi.org/10.1093/alcalc/37.5.451
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4572015-05-19HighWireOUPalcalc:37:5
HIGH PREVALENCE, PERSISTENT HAZARDOUS DRINKING AMONG NEW ZEALAND TERTIARY STUDENTS
Kypri, Kypros
Langley, John D.
McGee, Rob
Saunders, John B.
Williams, Sheila
Human Studies
<b>Aims:</b> To determine the prevalence of hazardous drinking and alcohol-related negative consequences in New Zealand tertiary students, and to identify predictors of hazardous drinking across a 6-month period. <b>Methods:</b> A total of 1480 tertiary students living in halls of residence was surveyed at the start of the academic year, and a subsample of 967 students was followed up 6 months later. Questionnaire items included quantity and frequency of drinking, alcohol-related problems, use of other substances, and the Alcohol Use Disorders Identification Test (AUDIT). Drinking at follow-up was modelled using demographic characteristics, mental well-being, other substance use, alcohol-related problems, and hall drinking norms, measured at baseline. <b>Results:</b> Among drinkers, mean (± SD) weekly consumption was 243 ± 241 and 135 ± 157 g of ethanol for males and females respectively. The majority of male (60.0%) and female (58.2%) drinkers typically consumed more than national safe drinking guidelines. Mean (± SD) AUDIT scores were 10.9 ± 7.6 for males and 7.6 ± 5.9 for females. After controlling for AUDIT scores at baseline, increased AUDIT scores at follow-up were higher with lower age, Maori ethnicity, smoking, cannabis use, high levels of alcohol-related negative consequences, and higher levels of drinking in the student’s hall of residence. <b>Conclusions:</b> Hazardous drinking is widespread and persistent among students living in the halls of residence. There is a need for university alcohol policies and intervention approaches among New Zealand tertiary students.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/457
http://dx.doi.org/10.1093/alcalc/37.5.457
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4652015-05-19HighWireOUPalcalc:37:5
INTERPRETATION OF ITEMS IN THE AUDIT QUESTIONNAIRE
Kypri, Kypros
McGee, Rob
Saunders, John B.
Langley, John D.
Dean, Johanna I.
Human Studies
— <b>Aims:</b> To test for the possibility that tertiary students misinterpret certain items on the Alcohol Use Disorders Identification Test (AUDIT). <b>Methods:</b> Responses to alternative question wordings were compared with responses to standard items. <b>Results:</b> Alterations to items 5 and 9, so that consequences of drinking epitomized in these items were more specifically defined, resulted in markedly different response distributions to the item, but the total AUDIT score was not changed. <b>Conclusions:</b> Caution is necessary before using individual AUDIT items as measures of consequences in population surveys, and the possibility of false positives in total scores should be borne in mind.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/465
http://dx.doi.org/10.1093/alcalc/37.5.465
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4682015-05-19HighWireOUPalcalc:37:5
ALCOHOL AND/OR OTHER DRUG USE AMONG ADULT NON-OCCUPANT MOTOR VEHICLE CRASH VICTIMS
Weber, Jim Edward
Maio, Ronald F.
Blow, Frederic C.
Hill, Elizabeth M.
Barry, Kristen L.
Waller, Patricia F.
Human Studies
— <b>Aims:</b> To identify the frequency of current or lifetime history of alcohol and/or other drug (AOD) use among the full range (admitted and discharged) of injured bicyclists and pedestrians involved in motor vehicle crashes. <b>Methods:</b> In a prospective study of non-occupant motor vehicle crash (NOMVC) victims ≥18 years over a 29-month period, blood was obtained for alcohol and drug testing. Current alcohol abuse/alcohol dependence (AA/AD) or drug abuse/drug dependence (DA/DD) was based on the Diagnostic Interview Survey. <b>Results:</b> In all, there were 108 NOMVC victims. Eleven per cent were alcohol (+), 7% drug (+), and 3% both. Sixteen per cent were AA/AD (+), 2.7% DA/DD (+), and 1.4% both. <b>Conclusions:</b> A substantial portion of patients with NOMVC injuries tested AOD (+) and had a current or lifetime substance abuse (AA/AD; DA/DD) diagnosis.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/468
http://dx.doi.org/10.1093/alcalc/37.5.468
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4722015-05-19HighWireOUPalcalc:37:5
HYPOURICAEMIA AS A MARKER OF A GENERALIZED PROXIMAL TUBULAR DAMAGE IN ALCOHOLIC PATIENTS
Liberopoulos, Evagelos
Miltiadous, George
Elisaf, Moses
CASE REPORT
— <b>Aims and Methods:</b> Hypouricaemia is not frequently encountered in alcoholic patients. Described herein is the case of a 69-year-old alcoholic patient. <b>Results:</b> The patient presented with severe hypouricaemia (serum uric acid 95.2 μmol/l) due to renal urate wasting associated with a cluster of other metabolic abnormalities in the context of a reversible generalized dysfunction of the proximal tubules that mimicked Fanconi syndrome. <b>Conclusions:</b> The underlying mechanisms of this rare presentation are discussed.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/472
http://dx.doi.org/10.1093/alcalc/37.5.472
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4772015-05-19HighWireOUPalcalc:37:5
INTRODUCTION
Colombo, Giancarlo
Gessa, Gian Luigi
PROCEEDINGS OF A SYMPOSIUM ENTITLED: 'GABA<sub>B</sub> RECEPTORS'
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/477
http://dx.doi.org/10.1093/alcalc/37.5.477
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4782015-05-19HighWireOUPalcalc:37:5
A POTENTIAL ROLE FOR GABAB AGONISTS IN THE TREATMENT OF PSYCHOSTIMULANT ADDICTION
Brebner, Karen
Childress, Anna Rose
Roberts, David C. S.
PROCEEDINGS OF A SYMPOSIUM ENTITLED: 'GABA<sub>B</sub> RECEPTORS'
— <b>Aims:</b> Here we briefly review the preclinical and clinical evidence that γ-aminobutyric acid (GABA<inf>B</inf>) agonists may be useful in the treatment of cocaine addiction. An extensive series of studies in rats has demonstrated that baclofen and other GABA<inf>B</inf> agonists reduce cocaine self-administration in an apparently specific manner. <b>Methods:</b> A number of schedules of reinforcement, including fixed-ratio, progressive-ratio and discrete trials procedures, have been used to model various aspects of cocaine reinforcement and addiction. <b>Results:</b> The results show that systemic pretreatment with baclofen can reduce cocaine intake at doses that do not affect responding for other positive reinforcers, such as food. Direct intracerebral injections of baclofen into the ventral tegmental area also produce a specific reduction in cocaine self-administration, suggesting that an inhibition of dopaminergic neurons may be responsible for the effect. Recent clinical evidence and case reports indicate some therapeutic value for baclofen in controlling cocaine intake and craving, although the evidence from controlled clinical trials has been less than convincing. Perhaps the most intriguing data come from human imaging studies, wherein cocaine addicts report increased cocaine craving and activation of orbital–frontal cortex, anterior cingulate and amygdala when shown videotapes of drug paraphernalia and other addicts taking cocaine. The craving is reduced and the limbic activation is eliminated in cocaine-dependent patients who had been taking baclofen (10–20 mg twice daily) for 7–10 days. <b>Conclusions:</b> Systematic clinical studies of GABA<inf>B</inf> agonists are needed to determine the extent to which these drugs might serve as tools to promote abstinence in cocaine users seeking treatment for their addiction. Several areas must still be addressed, including potential side-effects that may limit compliance and whether GABA<inf>B</inf> agonists interfere with other, non-drug-related behaviours.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/478
http://dx.doi.org/10.1093/alcalc/37.5.478
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4852015-05-19HighWireOUPalcalc:37:5
GABAergic MECHANISMS OF OPIATE REINFORCEMENT
Xi, Zheng-Xiong
Stein, Elliot A.
PROCEEDINGS OF A SYMPOSIUM ENTITLED: 'GABA<sub>B</sub> RECEPTORS'
The neurobiological mechanisms of opiate-induced reinforcement are still not completely understood. Over the past two decades, the vast majority of studies have focused on the role of the mesolimbic dopamine (DA) system. However, current studies strongly suggest that opiate actions on γ-aminobutyric acid (GABA)-ergic cells in both the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) appear to play critical roles. In this review, we focus on the neurochemical substrates of opiate reinforcement and review the role of DA and non-DA substrates, including opioid, GABA, glutamate and serotonin on opiate-reinforced behaviour and the activity of dopaminergic and GABAergic neurons in the VTA and the NAcc.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/485
http://dx.doi.org/10.1093/alcalc/37.5.485
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4952015-05-19HighWireOUPalcalc:37:5
BACLOFEN ANTAGONIZES INTRAVENOUS SELF-ADMINISTRATION OF NICOTINE IN MICE AND RATS
Fattore, Liana
Cossu, Gregorio
Martellotta, Maria Cristina
Fratta, Walter
PROCEEDINGS OF A SYMPOSIUM ENTITLED: 'GABA<sub>B</sub> RECEPTORS'
— <b>Aims:</b> γ-Aminobutyric acid (GABA)-ergic transmission plays an important role in modulating reinforcing effects of different drugs of misuse. In particular, stimulation of GABA<inf>B</inf> receptors negatively influences self-administration of cocaine, heroin, nicotine, alcohol and γ-hydroxybutyric acid. The effect and specificity of the GABA<inf>B</inf> agonist baclofen on nicotine misuse were studied on two animal models of self-administration. <b>Methods:</b> The effects of RS baclofen and the two isomers R baclofen and S baclofen were studied on the acute nicotine self-administration in drug-naïve mice. The effect of RS baclofen was also studied in rats trained to chronically self-administer nicotine under a continuous reinforcement (FR1) schedule. <b>Results:</b> RS baclofen antagonizes nicotine intravenous self-administration at doses of 1.25–2.5 mg/kg intraperitoneally (i.p.). Furthermore, this effect is sterospecific. R baclofen completely prevented nicotine self-administration at the dose of 0.625 mg/kg i.p., whereas S baclofen was inactive up to the dose of 2.5 mg/kg i.p. In rats trained to self-administer nicotine, pretreatment with RS baclofen at the dose of 2.5 mg/kg i.p. significantly increased the rate of responding for nicotine. This effect was similar to the effect obtained when rats were pretreated with the nicotine central receptor antagonist mecamylamine (1 mg/kg i.p.). <b>Conclusions:</b> These data show that baclofen is able to antagonize nicotine-rewarding effects in mice and rats and suggest its potential clinical utility for the treatment of nicotine misuse.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/37/5/495
http://dx.doi.org/10.1093/alcalc/37.5.495
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/4992015-05-19HighWireOUPalcalc:37:5
THE GABAB RECEPTOR AGONISTS BACLOFEN AND CGP 44532 PREVENT ACQUISITION OF ALCOHOL DRINKING BEHAVIOUR IN ALCOHOL-PREFERRING RATS
Colombo, Giancarlo
Serra, Salvatore
Brunetti, Giuliana
Atzori, Giuliana
Pani, Marialaura
Vacca, Giovanni
Addolorato, Giovanni
Froestl, Wolfgang
Carai, Mauro A. M.
Gessa, Gian Luigi
PROCEEDINGS OF A SYMPOSIUM ENTITLED: 'GABA<sub>B</sub> RECEPTORS'
— <b>Aims:</b> The present study investigated the effect of the γ-aminobutyric acid (GABA)<inf>B</inf> receptor agonists, baclofen and CGP 44532, on the acquisition of alcohol drinking behaviour in selectively bred Sardinian alcohol-preferring (sP) rats. <b>Methods:</b> Baclofen [0, 1 and 3 mg/kg, intraperitoneally (i.p.)] and CGP 44532 (0, 0.1, 0.3 and 1 mg/kg, i.p.) were administered immediately before alcohol presentation to alcohol-naive sP rats. Alcohol was offered under the two-bottle free-choice regimen with unlimited access for 24 h/day. Drug treatment was repeated once daily for 10 consecutive days. <b>Results:</b> Baclofen and CGP 44532, dose-dependently and with comparable efficacy, suppressed alcohol intake; compensatory increases in water intake left total fluid intakes virtually unchanged. <b>Conclusions:</b> These results demonstrate that baclofen and CGP 44532 prevent the acquisition of alcohol drinking behaviour in sP rats, and suggest the involvement of the GABA<inf>B</inf> receptor in the mechanisms underlying the disclosure and experience of the reinforcing properties of alcohol in this rat line.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/499
http://dx.doi.org/10.1093/alcalc/37.5.499
en
Copyright (C) 2002, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:37/5/5042015-05-19HighWireOUPalcalc:37:5
BACLOFEN EFFICACY IN REDUCING ALCOHOL CRAVING AND INTAKE: A PRELIMINARY DOUBLE-BLIND RANDOMIZED CONTROLLED STUDY
Addolorato, Giovanni
Caputo, Fabio
Capristo, Esmeralda
Domenicali, Marco
Bernardi, Mauro
Janiri, Luigi
Agabio, Roberta
Colombo, Giancarlo
Gessa, Gian Luigi
Gasbarrini, Giovanni
PROCEEDINGS OF A SYMPOSIUM ENTITLED: 'GABA<sub>B</sub> RECEPTORS'
— <b>Aims:</b> The γ-aminobutyric acid (GABA<inf>B</inf>) receptor agonist, baclofen, has recently been shown to reduce alcohol intake in alcohol-preferring rats and alcohol consumption and craving for alcohol in an open study in humans. The present study was aimed at providing a first evaluation of the efficacy of baclofen in inducing and maintaining abstinence and reducing craving for alcohol in alcohol-dependent patients in a double-blind placebo-controlled design. <b>Methods:</b> A total of 39 alcohol-dependent patients were consecutively enrolled in the study. After 12–24 h of abstinence from alcohol, patients were randomly divided into two groups. Twenty patients were treated with baclofen and 19 with placebo. Drug and placebo were orally administered for 30 consecutive days. Baclofen was administered at the dose of 15 mg/day for the first 3 days and 30 mg/day for the subsequent 27 days, divided into three daily doses. Patients were monitored as out-patients on a weekly basis. At each visit alcohol intake, abstinence from alcohol, alcohol craving and changes in affective disorders were evaluated. <b>Results:</b> A higher percentage of subjects totally abstinent from alcohol and a higher number of cumulative abstinence days throughout the study period were found in the baclofen, compared to the placebo, group. A decrease in the obsessive and compulsive components of craving was found in the baclofen compared to the placebo group; likewise, alcohol intake was reduced in the baclofen group. A decrease in state anxiety was found in the baclofen compared to the placebo group. No significant difference was found between the two groups in terms of current depressive symptoms. Baclofen proved to be easily manageable and no patient discontinued treatment due to the presence of side-effects. No patient was affected by craving for the drug and/or drug abuse. <b>Conclusions:</b> Baclofen proved to be effective in inducing abstinence from alcohol and reducing alcohol craving and consumption in alcoholics. With the limits posed by the small number of subjects involved, the results of this preliminary double-blind study suggest that baclofen may represent a potentially useful drug in the treatment of alcohol-dependent patients and thus merits further investigations.
Oxford University Press
2002-09-01 00:00:00.0
TEXT
text/html
http://alcalc.oxfordjournals.org/cgi/content/short/37/5/504
http://dx.doi.org/10.1093/alcalc/37.5.504
en
Copyright (C) 2002, Medical Council on Alcohol