Safety and tolerability of N-acetylcysteine in cocaine-dependent individuals.

A double-blind placebo-controlled crossover Phase I trial was conducted to assess the safety and tolerability of N-Acetylcysteine (NAC) in healthy, cocaine-dependent humans. Thirteen participants attended a three-day hospitalization in which they received placebo or NAC. Subjects were crossed over to receive the opposite medication condition during a second three-day hospitalization, which occurred the following week.

From blue states to up states: a regional view of NMDA-ethanol interactions.

This article summarizes the proceedings of a symposium at the 2005 Research Society on Alcoholism Meeting in Santa Barbara, California, organized and cochaired by John J. Woodward and Dorit Ron. The purpose of the symposium was to discuss recent findings that extend our understanding of the importance of the N-methyl-D-aspartate (NMDA) receptor as a target for ethanol action in the brain.

Alcohol biomarker screening in medical and surgical settings.

This article highlights the proceedings of a symposium presented at the 28th Annual Meeting of the Research Society on Alcoholism in Santa Barbara, CA, on June 28, 2005, organized and chaired by Peter Miller. The presentations included (1) Screening for Alcohol Use Disorders in Surgical and Trauma Patients, presented by Claudia Spies; (2) Are Serum Levels of %CDT and GGT Related to Severity of Liver Biopsy Inflammation, Fibrosis, and Steatohepatitis in Patients with Hepatitis C? by Martin Javors; (3) Biochemical Alcohol Screening in the Treatment of Hypertension, presented by Peter Miller; and (4) The Cost-Effectiveness of a New Biomarker, CDT, in a Primary Care Sample, by Michael Fleming. Presentations were discussed by Raymond Anton.

Personality correlates of startle habituation.

This study investigated the relationship between extraversion and rates of acoustic startle habituation, a potential biological marker for individual differences. Personality was measured using the Eysenck Personality Questionnaire (EPQ), the Sensation Seeking Scale (SSS), and Tellegen's Multidimensional Personality Questionnaire (MPQ). Higher EPQ Extraversion and higher SSS scores were associated with faster, more rapid startle habituation.

Partial deletion of glial cell line-derived neurotrophic factor (GDNF) in mice: Effects on sucrose reward and striatal GDNF concentrations.

Glial cell line derived neurotrophic factor (GDNF) has been reported to alter the reward value of abused substances such as alcohol and cocaine as well as neural circuitry underlying reward. The role of GDNF in reward was further characterized in the present study using operant procedures to determine the value of a natural reward, sucrose, in GDNF heterozygous (GDNF+/-) mice versus wild-type (WT) mice. Female mice were tested for 2 h daily for 10 days in operant chambers with 2 levers.

Lorazepam and MK-801 effects on behavioral and electrographic indices of alcohol withdrawal sensitization.

Repeated cycles of chronic ethanol exposure and withdrawal result in sensitization of withdrawal-related CNS hyperexcitability that generally reflects an imbalance in activity of GABA and glutamate systems. Many pharmacological treatments for ethanol withdrawal target neuroadaptive changes in GABA and glutamate neurotransmission. The present study utilized a mouse model of repeated withdrawals to evaluate the ability of lorazepam and MK-801 treatments to antagonize behavioral and electroencephalographic (EEG) measures of sensitized withdrawal seizure activity.

Clinical implications of continued alcohol consumption after diagnosis of upper aerodigestive tract cancer.

Aims: To examine clinical implications of findings on the relationship between continued alcohol consumption in patients after diagnosis and treatment of upper aerodigestive tract cancer.

Methods: Clinical research literature on the prevalence and effects of alcohol consumption after oral cancer diagnosis was reviewed. Since limited research is currently available on this important clinical topic, all published studies were considered regardless of size and methodology.

The influence of sex on extracellular dopamine and locomotor activity in C57BL/6J mice before and after acute cocaine challenge.

C57BL6/J (C57) mice serve as a useful animal model of cocaine abuse because they self-administer cocaine, exhibit place conditioning to cocaine, discriminate the interoceptive cues of cocaine, and are used for backcrossing strains of genetically modified mice. The present study was to examine the influence of sex on extracellular DA and locomotor activity in C57 mice in response to acute cocaine challenge. In the first experiment, male and female mice were implanted with guide cannulae aimed at the dorsal striatum.

The A-OCDS predicts both craving and alcohol cue reactivity in adolescent alcoholics.

Adolescents with alcohol dependence may experience marked craving and physiologic reactivity in the presence of alcohol cues which could undermine treatment gains. The Adolescent Obsessive Compulsive Drinking Scale (A-OCDS) was developed to help quantify the severity of alcohol craving in adolescents with alcohol use disorders. The A-OCDS is a relatively new instrument, and empirical data are needed to support its value in clinical trials.

Excessive alcohol consumption and hypertension: clinical implications of current research.

Substantial evidence demonstrates that: 1) heavy alcohol consumption (three or more standard drinks per day) is associated with and predictive of hypertension; 2) reduction in alcohol consumption is associated with a significant dose-dependent lowering of mean systolic and diastolic blood pressure; and 3) physician advice can reduce heavy drinking in hypertensive patients. These findings suggest that the routine evaluation of alcohol consumption in hypertensive patients is warranted. The Alcohol Use Disorders Identification Test-C (AUDIT-C), a brief, three-question screening test, is useful in this regard.

Alcohol cue reactivity in alcohol-dependent adolescents.

Objective: There is substantial evidence that adults with alcohol dependence show different responses (increased craving, increased salivation, changes in heart rate) to alcohol-related stimuli (i.e., alcohol cue reactivity) than nonalcoholics.

Genetic variation in heroin-induced changes in behaviour: effects of B6 strain dose on conditioned reward and locomotor sensitization in 129-B6 hybrid mice.

Substantial interindividual variability exists in the propensity to develop opiate addiction. Genetic variation in opiate reward may contribute to this variability. A large body of evidence indicates genetic variation in mice for several effects of opiate drugs.

The effects of alcohol preexposure on cocaine, alcohol and cocaine/alcohol place conditioning.

The present experiment examined the effects of alcohol preexposure on place conditioning with cocaine, alcohol or the cocaine/alcohol combination. Specifically, 91 male Sprague-Dawley rats were injected i.p.

Fyn kinase does not reduce ethanol inhibition of zinc-insensitive NR2A-containing N-methyl-D-aspartate receptors.

N-methyl-D-aspartate (NMDA) receptors are ion channels activated by the neurotransmitter glutamate and are important mediators of neuronal signal transduction. Ethanol inhibits ion flux through NMDA receptors at concentrations that are associated with behavioral signs of intoxication. The overall sensitivity of NMDA receptors to ethanol is influenced by factors, including subunit composition and interactions with cytoskeletal elements.

Inhibition of gap junction currents by the abused solvent toluene.

Abused inhalants are a large class of compounds that are inhaled for their intoxicating and mood altering effects. They include chemicals with known therapeutic uses such as anesthetic gases as well as volatile organic solvents like toluene that are found in paint thinners and adhesives. Because of their widespread commercial use and availability, inhalants are often among the first drugs that children encounter and use of these compounds is often associated with adverse acute and long-term consequences.

Tiagabine reduces ethanol reward in C57BL/6 mice under acute and chronic administration regimens.

Three experiments conducted on male C57BL/6 (B6) mice examined the effects of subcutaneous injections of the GABA uptake inhibitor, tiagabine, on appetitive (lever responding) and consummatory behavior (fountain contacts) of food restricted B6 mice for 12% ethanol and water rewards (Exp-1), and for food reward (Exp-2) delivered on a fixed ratio 4 schedule of reinforcement. Effects of acute injections (1,3,6,9 mgkg) and chronic administration (6,9 mg/kg) was examined. Exp-3 examined tiagabine effects on the voluntary consumption of continuously available 12% ethanol, and on the interactive effects of tiagabine and ethanol on motor activity of non-food restricted B6 mice.

Treatment of alcohol withdrawal.

Appropriate treatment of alcohol withdrawal (AW) can relieve the patient's discomfort, prevent the development of more serious symptoms, and forestall cumulative effects that might worsen future withdrawals. Hospital admission provides the safest setting for the treatment of AW, although many patients with mild to moderate symptoms can be treated successfully on an outpatient basis. Severe AW requires pharmacological intervention.

Attentional bias and drinking to cope with social anxiety.

This study investigated the sensitivity of the emotional Stroop test for identifying individuals who reported drinking to cope with social fears. Community volunteers completed a modified Stroop task during which social threat, alcohol-related, and control words were presented. High scores on drinking-to-cope measures were hypothesized to be associated with longer response latencies to both social threat and alcohol-related words.

Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice.

Background: The development of dependence may have significant motivational consequences regarding continued use and abuse of ethanol. We have developed a mouse model of ethanol dependence and repeated withdrawals that demonstrates sensitization of seizures and other symptoms of withdrawal. It is unclear whether such experience influences ethanol drinking behavior.

Incorporating social anxiety into a model of college student problematic drinking.

College problem drinking and social anxiety are significant public health concerns with highly negative consequences. College students are faced with a variety of novel social situations and situations encouraging alcohol consumption. The current study involved developing a path model of college problem drinking, including social anxiety, in 316 college students referred to an alcohol intervention due to a campus alcohol violation.

Alterations in glutamatergic and gabaergic ion channel activity in hippocampal neurons following exposure to the abused inhalant toluene.

Toluene, a representative member of the large class of abused inhalants, decreases neuronal activity and depresses behavior in both animals and humans. The sites of action of toluene are not completely known but recent studies suggest that ion channels that regulate neuronal excitability may be particularly sensitive. Previous studies with recombinant receptors showed that toluene decreases currents carried by N-methyl-D-aspartate (NMDA)-glutamate receptors without affecting those gated by non-NMDA receptors.

Diagnosis and treatment of co-occurring affective disorders and substance use disorders.

There is growing interest in the co-occurrence of mood and substance use disorders. It is clear that co-occurrence of these disorders is common and has an impact on prognosis and course of both disorders. The diagnostic issues at the interface of substance or alcohol use disorders and affective illnesses are particularly difficult because of the substantial symptom overlap between substance intoxication and withdrawal and symptoms of affective disorders.

The dopamine D1 antagonist reduces ethanol reward for C57BL/6 mice.

Background: Dopamine D1 antagonist effects on behaviors related to obtaining and consuming ethanol remain unclear. The highly selective D1 antagonist ecopipam (SCH 39166), which has no effect on the serotonin system, was used to evaluate the role of D1 receptors in ethanol reward and its potential for treating alcohol abuse by determining its effect on several measures of ethanol reward in C57BL/6 (B6) mice.

Methods: Ecopipam (0.

Self-report and biomarker alcohol screening by primary care physicians: the need to translate research into guidelines and practice.

Aims: To assess knowledge and use of alcohol self-report and biomarker screening by physicians.

Methods: Forty-eight primary care physicians were surveyed.

Results: Knowledge of MCV and GGT was as good as that for non-biomarker screening tools (CAGE, AUDIT) although use was significantly less.

The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: deficits in cognitive function.

The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze.