bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for glutamate transmission in addiction to psychostimulants
Authors: Kalivas Peter W. 
Published: October 2006

AbstractPsychostimulant addiction results in the emergence of undesirable behaviors such as drug craving and paranoia. Using animal models of addiction the neurobiological substrates mediating these behaviors have been examined. Studies have focused on cellular adaptations within the motive circuit that contains the nucleus accumbens, ventral tegmental area, ventral pallidum and prefrontal cortex. While long‐term alterations in dopamine transmission have been clearly characterized, more recent studies reveal that important neuroadaptations are also produced in glutamate transmission.This short review provides a description of these neuroadaptations and a discussion of how these psychostimulant‐induced changes may synergize to elicit addiction‐related behaviors.
Role of peroxynitrite in methamphetamine‐induced dopaminergic neurotoxicity and sensitization in mice
Authors: Ali Syed F. , Haung Paul , Itzhak Yossef 
Published: October 2006

AbstractMethamphetamine (METH)‐induced dopaminergic neurotoxicity is thought to be associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recently, we have reported that copper/zinc(CuZn)‐superoxide dismutase transgenic mice are resistant to METH‐induced neurotoxicity. In the present study, we examined the role of the neuronal nitric oxide synthase (nNOS), susceptibility of nNOS knockout (KO) mice and sensitization to psychostimulants after neurotoxic doses of METH. Male SwissWebster mice were treated with or without 7‐nitroindazole (7‐NI) along with METH (5 mg/kg,ip,q 3h × 3) and were sacrificed 72 h after the last METH injection. Dopamine (DA) and dopamine transporter (DAT) binding sites were determined in striatum from saline and METH‐treated animals. 7‐NI completely protected against the depletion of DA, and DAT in striatum. In follow‐up experiments nNOS KO mice along with appropriate control (C57BL/6N, SV129 and B6JSV129) mice were treated with METH (5 mg/kg,ip, q 3h × 3) and were sacrificed 72 h after dosing. This schedule of METH administrations resulted in only 10–20% decrease in tissue content of DA and no apparent change in the number of DAT binding sites in nNOS KO mice. However, this regime of METH resulted in a significant decrease in the content of DA as well as DAT binding sites in the wild‐type animals. Pre‐exposure to single or multiple doses of METH resulted in a marked locomotion sensitization in response to METH. However, the nNOS KO mice show no sensitization in response to METH after single or multiple injections of METH. Therefore, these studies strongly suggest the role of peroxynitrite, nNOS and DA system in METH‐induced neurotoxicity and behavioral sensitization.
Molecular and regional targets of cocaine in primate brain: liberation from prosaic views
Authors: Madras Bertha K. , Miller Gregory M. , Meltzer Peter C. , Brownell Anna‐Liisa , Fischman Alan J. 
Published: October 2006

AbstractThe neurochemical processes underlying initial exposure to and reinforcing effects of cocaine are not fully understood. An enduring hypothesis of cocaine addiction is based on an underlying premise that dopamine is the acute mediator of the rewarding effects of cocaine and this nefarious role extends through each phase of addiction. Cocaine is an effective inhibitor of the dopamine transporter, thereby increasing extracellular dopamine levels. Euphoria is attributed to the cocaine‐induced inundation of extracellular dopamine and the withdrawal and craving for cocaine after cessation of drug use are attributed to neuroadaptive processes to dampen dopaminergic transmission. Nevertheless, our understanding of the role of dopamine transporter blockade in cocaine addiction is not fully understood. The objectives of this laboratory are to investigate the primary targets of cocaine in the brain, those associated with the initial phase of cocaine use and that can provide leads for investigating neuroadaptive processes that may trigger addiction. Two prosaic views of the neurobiology of cocaine addiction are examined in this review. The first is based on the assumption that the dopamine transporter contributes significantly to the stimulant and reinforcing effects of cocaine, and focuses on how stimulant drugs of abuse such as cocaine bind to the dopamine transporter. We present evidence that the widespread assumption that dopamine transporter blockers require an amine nitrogen in their structure is incorrect as non‐amines are effective blockers of transporters. The second prosaic view, based on the assumption that the dopamine transporter fulfills a paramount role in cocaine addiction, is assessed in view of mounting evidence that the transporter may not account for the full spectrum of cocaine's effects. Other targets of cocaine, which may be relevant to the acute and chronic effects of cocaine, are presented.
Book and media reviews
Authors: COOK CHRIS 
Published: October 2006

Books reviewed in this article:Book reviews in this column will primarily be of titles focusing completely, or in part, on biological aspects of addiction. However, significant titles of general relevance to the addictions field will also be included, even if they are not “biologi cal”, as will titles of general methodological and clinical relevance, even if they are not on “addictions”. Similar considerations will apply to other media (software, audio tapes and CDs, videos, etc). However, specific “addictions” software applications seem to be relatively uncommon and, as these items are rarely reviewed elsewhere, we will endeavour to include reviews of some of the older programmes that are still useful, as well as new titles that appear. I would appreciate suggesti ons of any items suitable for reviews, but especially software and other media of specific relevance to the addictions. Please contact: Dr David Ball, National Addiction Centre, 4 Windsor Walk, London SE5 8AF, UK. Evaluating the Treatment of Drug Abuse in the European Union. EMCDDA scientific monograph series no. 3 Genetics and Criminality. The Potential Misuse of Scientific Information in Court JEFFREY R. BOTKIN, WILLIAM M. McMAHON & LESLIE PICKERING Dimensions of Forgiveness, Psychological Research and Theological Perspectives EVERETT L. WORTHINGTON Jr Handbook of Psychiatry for Primary Care C. W. ALLWOOD & C. A. GAGIANO Scientific Unit Conversion, 2nd edn FRANÇOIS CARDARELLI (English translation by M.J. SHIELDS)
Gamma‐hydroxybutyric acid in alcohol preference, dependence and withdrawal
Authors: Colombo Giancarlo , Gessa Gian Luigi 
Published: October 2006

AbstractGamma‐hydroxybutyric acid (GHB) is an endogenous constituent of the mammalian brain, where it likely functions as a neurotransmitter or a neuromodulator. Its exogenous administration exerts a number of pharmacological effects, including reduction of intensity of alcohol withdrawal syndrome and alcohol consumption in both laboratory animals and human alcoholics.The clinical studies conducted to date, although often testing samples of limited size, feature GHB as an effective, well‐tolerated and safe drug for the treatment of alcohol dependence. Behavioural data in rats suggest that GHB may produce alcohol‐like effects. This similarity may explain why GHB produces positively reinforcing properties, being subsequently self‐administered by rodents and sometimes abused by humans (although episodes of self‐directed intake of GHB appear to be a limited phenomenon in alcoholics); in addition it provides support to the hypothesis that GHB constitutes for alcoholism a replacement therapy similar to methadone in heroin addiction.
Harman and norharman plasma levels in weaned alcoholics: correlations with depression and tobacco smoking
Authors: Kiefer F. , Krödel A. , Jahn H. , Wolf K. , Barocka A. 
Published: October 2006

AbstractBased on the hypothesis that β‐carbolines are involved in the pathogenesis of alcohol‐related mood disturbance, harman and norharman levels were assayed in the blood plasma of alcoholics and correlated to the Hamilton Depression (HAM‐D) scores after 3 and 5 weeks post‐admission. Tobacco smoking was co‐evaluated since it is known to influence β‐carboline levels. After a 3‐week period, plasma harman but not norharman was increased in depressed alcoholics and positively related to the HAM‐D sum‐score (r = 0.47; p < 0.04) and to tobacco smoking (r = 0.56; p < 0.02). Since no correlation between depression and smoking was found, these data could account for the higher incidence of depressive symptoms in withdrawn alcoholics with increased harman levels. The partial correlations support this hypothesis.
A compressed opiate detoxification regime with naltrexone maintenance: patient tolerance, risk assessment and abstinence rates
Authors: Beaini A. Y. , Johnson T. S. , Langstaff P. , Carr M. P. , Crossfield J. N. , Sweeney R. C. 
Published: October 2006

AbstractOpiate detoxification using methadone programmes are inefficient and expensive. Rapid and ultra‐rapid detoxification using precipitated withdrawal under heavy sedation or anaesthesia provide increased efficiency and speed, but are limited by the requirement for high‐dependency facilities and are perceived as high‐risk procedures. Procedures using precipitated withdrawal over longer periods with lower sedation are safer, but 20% of patients fail to tolerate these. Here we evaluate a naltrexone compressed opiate detoxification (NCOD) protocol. We investigated patient acceptance, organ function and abstinence rates on 504 consecutive patients undergoing treatment at the Harrogate Detox5 centre between February 1996 and January 1999. Ninety‐eight per cent of patients completed the procedure; 81% of patients reported withdrawal was “better than expected”. Only 3% of patients reported any pain. Laboratory investigations demonstrated no organ dysfunction. Abstinence rates post‐detox were high with 71%, 61% and 51% of patients free of opiates 3, 6 and 12 months post‐detox, respectively. Compliance with the naltrexone maintenance in abstinent patients was 66%, 68% and 30% at these time points. This NCOD protocol provides an efficient method of detoxifying opiate abusers with little patient discomfort or risk to health. Abstinence rates are better than those in comparable studies using other programmes.
Chronic ethanol treatment and GABA A receptor a6 subunit gene expression: a study using a6 subunit‐deficient mice
Authors: Vekovischeva Olga Y. , Uusi‐Oukari Mikko , Korpi Esa R. 
Published: October 2006

AbstractChronic alcohol administration increases the expression of cerebellum‐specific GABA A receptor α6 subunit mRNA, protein and selective autoradiographical fingerprint on rat and mouse brain sections. We have tested whether the α6 gene is activated by chronic alcohol administration (daily p.o. injection of 2 g/kg during the first 3 days and 2.5 g/kg during the next 17 days) that produced tolerance in the rotarod test to motor impairment by acute challenge of ethanol (2 g/kg, i.p.). We utilized a mouse line engineered to express E. coli b‐galactosidase enzyme and an unfunctional truncated α6 subunit under the control of the α6 gene promoter. Chronic ethanol treatment failed to alter the cerebellar b‐galactosidase activity when compared with no treatment and isocaloric sucrose treatment in groups of α6 subunit‐deficient mice. The results suggest that tolerance to motor‐impairing effects of ethanol can be achieved in the absence of α6 subunit‐containing GABA A receptors, but that the reported upregulation of α6 gene transcription by ethanol treatment requires functional α6 subunits.
Leptin is associated with craving in females with alcoholism
Authors: Kraus T , Reulbach U , Bayerlein K , Mugele B , Hillemacher T , Sperling W , Kornhuber J , Bleich S 
Published: October 2006

AbstractThe appetite and weight regulating peptide leptin was associated recently with alcohol craving during withdrawal. Nevertheless, correlations were only significant with craving displayed on the visual analogue scale for maximum craving during the previous week (VAS), and not if assessed with the highly validated Obsessive Compulsive Drinking Scale (OCDS). The objective of the following study, therefore, is to elucidate further the associations between the leptin system and craving concepts during alcohol withdrawal. A sufficiently large sample size should allow multiple statistical subgroup and confounder analyses. We prospectively investigated 102 chronic alcoholic inpatients (23 females, 79 males) during withdrawal on days 0 (admission), 1, 2 and days 7 ‐ 10. In addition to the statistical analysis of the total sample, females and males were to be analysed separately. For detecting associations between leptin levels and craving scores multiple regression analysis was performed. Plasma leptin levels were determined, and craving for ethanol was assessed by both the OCDS and the VAS. Leptin plasma levels significantly increased during alcohol withdrawal compared to day 0, while all craving scores decreased. Body mass corrected leptin plasma levels predicted craving on day 0 in the OCDS total score (R  = 0.55, F  = 7.91, df = 1.19, p  < 0.05) and in the OCDS obsessive subscore (R  = 0.57, F < = 8.48, df = 1.19, p  < 0.05) in females. Neither in males nor in the total population did multiple regression analysis reveal any significant results. Leptin levels seem to change during inpatient alcohol withdrawal. In a multivariate model, correlations between leptin levels and the highly validated craving scores of the OCDS can only be assumed in females. Hence, gender differences have to be taken into account when searching for neurobiological models of alcohol craving.
The dopamine D2 receptor C32806T polymorphism (DRD2 Taq1A RFLP) exhibits no association with smoking behaviour in a healthy UK population
Authors: Johnstone EC , Yudkin P , Griffiths SE , Fuller A , Murphy M , Walton R 
Published: October 2006

AbstractA single nucleotide polymorphism (SNP) in the Taq1A site near the DRD2 gene has been associated in several studies with smoking behaviour. We genotyped 732 current smokers (241 low, one to nine cigarettes a day, 250 mid, 10 ‐ 19 cigarettes, 241 high, 20 + cigarettes) and 243 never‐smokers at this site (C32806T), to test for effects on smoking initiation and amount of tobacco consumed. No significant association between minor allele frequency and smoking status was detected. Multiple regression analysis including DRD2 genotype, sex, age and alcohol consumption as predictors showed that level of cigarette consumption was associated with sex (p  = 0.003) and age (p  = 0.002) but not with alcohol consumption (p  = 0.25) or DRD2 genotype (p  = 0.76).
REVIEW: The alcohol‐preferring P rat and animal models of excessive alcohol drinking
Authors: Bell Richard L. , Rodd Zachary A. , Lumeng Lawrence , Murphy James M. , McBride William J. 
Published: October 2006

ABSTRACTThe alcohol‐preferring, P, rat was developed by selective breeding to study ethanol drinking behavior and its consequences. Characterization of this line indicates the P rat meets all of the criteria put forth for a valid animal model of alcoholism, and displays, relative to their alcohol‐non‐preferring, NP, counterparts, a number of phenotypic traits associated with alcohol abuse and alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the sedative and aversive effects of ethanol and more sensitive to the stimulatory effects of ethanol. Neurochemically, research with the P line indicates the endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic systems may be involved in a predisposition for alcohol abuse and alcoholism. Paralleling the clinical literature, genetically selected P rats display levels of ethanol intake during adolescence comparable to that seen during adulthood. Binge drinking has been associated with an increased risk for health and other problems associated with ethanol abuse. A model of binge‐like drinking during the dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little as three 1‐hour access periods/day, which approximates the 24‐hour intake of P rats with free‐choice access to a single concentration of ethanol. The alcohol deprivation effect (ADE) is a transient increase in ethanol intake above baseline values upon re‐exposure to ethanol access after an extended period of deprivation. The ADE has been proposed to be an animal model of relapse behavior, with the adult P rat displaying a robust ADE after prolonged abstinence. Overall, these findings indicate that the P rat can be effectively used in models assessing alcohol‐preference, a genetic predisposition for alcohol abuse and/or alcoholism, and excessive drinking using protocols of binge‐like or relapse‐like drinking.
CLINICAL AND IMAGING STUDY: Imaging alcohol cue exposure in alcohol dependence using a PET 15O‐H2O paradigm: results from a pilot study
Authors: Lingford‐Hughes Anne R. , Daglish M. R. C. , Stevenson B. J. , Feeney A. , Pandit S. A. , Wilson Steven J. , Myles Judith , Grasby Paul M. , Nutt David J. 
Published: October 2006

ABSTRACTCraving is a commonly used term to describe an intense desire for a substance or behaviour; however, its underlying neurobiology is not fully characterized. We have successfully used a cue exposure paradigm with functional neuro‐imaging (H215O PET; PET, positron emission tomography) in abstinent opiate addicts. This study showed that salient cue exposure results in activation in the left anterior cingulate/mediofrontal cortex and elicited craving correlated with activity in the left orbitofrontal cortex. We therefore aimed to replicate this study in alcohol dependence to see if a similar pattern of neural activation occurred. We recruited six abstinent alcohol‐dependent and six non‐dependent subjects who each underwent a 12‐run PET scan using H215O to measure changes in regional blood flow during exposure to an alcoholic drink or its visually matched non‐alcoholic drink. Physiological data and subjective ratings were also recorded. Statistical parametric mapping (SPM99) was used to analyse the PET images. Compared with control subjects, abstinent alcohol‐dependent subjects rated their alcohol craving higher at baseline and throughout the study, but there was no significant change in the scores in response to the cues in either group. SPM analysis across all subjects showed significant activation in the occipital cortex in response to the alcohol cue as compared with the neutral one. Analysis of the same regions that were activated in the opiate study, revealed significant increases in signal activation in the left medial prefrontal area, but only in abstinent alcohol‐dependent subjects. In conclusion, in abstinent alcohol dependence we suggest that a simple cue exposure paradigm is not sufficiently powerful in functional imaging studies to determine the underlying neurobiology of subjective craving. Comparisons with the finding in opiate dependence suggest a shared region, the anterior cingulate/left medial prefrontal cortex is involved in the cue response in dependent subjects but not controls.
GENETIC STUDY: No association of dopamine receptor sensitivity in vivo with genetic predisposition for alcoholism and DRD2/DRD3 gene polymorphisms in alcohol dependence
Authors: Wiesbeck Gerhard A. , Dürsteler‐MacFarland Kenneth M. , Wurst Friedrich Martin , Walter Marc , Petitjean Sylvie , Müller Sandra , Wodarz Norbert , Böning Jobst 
Published: October 2006

ABSTRACTThis study sought to examine dopamine receptor sensitivity among alcoholics in vivo and to explore whether this sensitivity might be associated with functional variations of dopamine D2 (DRD2) and D3 (DRD3) receptor genes along with a genetic predisposition for alcoholism as reflected by an alcohol‐dependent first‐degree relative. We analyzed the −141C Ins/Del polymorphism in the promoter region of the DRD2 gene and the Ser9Gly (BalI) polymorphism in exon 1 of the DRD3 gene in 74 alcohol‐dependent Caucasian men with or without genetic predisposition for alcoholism. In vivo dopamine receptor sensitivity was assessed by measuring apomorphine‐induced growth hormone release. A three‐way analysis of variance revealed no significant effects of DRD2, DRD3 genotypes and genetic predisposition on dopamine receptor sensitivity. Given the explorative and preliminary character of this investigation, we cannot provide evidence that in alcohol‐dependent Caucasian men a genetic predisposition for alcoholism along with functional variants of the DRD2 and DRD3 genes are associated with differences in dopamine receptor sensitivity.
CLINICAL AND IMAGING STUDY: Glucocorticoid negative feedback in methadone‐maintained former heroin addicts with ongoing cocaine dependence: dose–response to dexamethasone suppression
Authors: Aouizerate Bruno , Ho Ann , Schluger James H. , Perret Guillaume , Borg Lisa , Le Moal Michel , Piazza Pier V. , Kreek Mary Jeanne 
Published: October 2006

ABSTRACTCombined cocaine and illicit opiate use is common. This study aimed to test the hypothesis that cocaine dependence in former heroin‐addicted patients maintained on methadone treatment is associated with enhanced glucocorticoid negative feedback. Multiple dose dexamethasone suppression tests, using a conventional 2.0 mg dose, and two lower doses, 0.5 mg and 0.125 mg, were performed in 10 methadone‐maintained former heroin addicts with ongoing cocaine dependence (C‐MM), 10 stabilized methadone‐maintained former heroin addicts with no ongoing drug or alcohol use (MM), and 22 normal volunteers (NV). At 9 hours, there was no difference in plasma adrenocorticotropin hormone (ACTH) and/or cortisol levels among groups on the baseline day, as well as after the two lower doses of dexamethasone. At 17 hours, C‐MM and MM had significantly lower plasma ACTH and/or cortisol levels than NV. However, C‐MM did not significantly differ from MM in their hormonal levels. When the hormonal responses to dexamethasone are expressed as magnitude of lowering from baseline, there was no significant difference at any dose among groups. Therefore, C‐MM exhibited a normal glucocorticoid negative feedback in the morning. Using the standard interpretation of dexamethasone suppression testing based on the examination of the actual hormonal levels rather than the difference from baseline condition, C‐MM appear to have glucocorticoid effects similar to MM, yet were both greater than NV in the late afternoon. Thus, further studies are needed to know whether altered glucocorticoid negative feedback is related to chronic cocaine exposure, or is the result of former heroin addiction and/or its long‐term treatment with methadone.