Journal of addiction research & therapy最新文献

BACKGROUND: Gender differences in the relationship between alcohol use and depressive symptoms are inconsistent, and few studies have addressed this issue in Russia. Because this finding may have important implications for interventions to reduce alcohol misuse or alcohol related problems in Russia, we conducted a study to investigate whether the association between alcohol use and depressive symptoms differs by gender at high risk for HIV. METHODS: We used the Alcohol Use Disorders Identification Test (AUDIT) and the 10-item Center for Epidemiological Studies Depression Scale to measure alcohol use and depressive symptoms among 307 patients who attended a clinic for sexually transmitted infections in St. Petersburg, Russia. Logistic regression models were applied for the analysis. RESULTS: The comparison of data between men and women revealed a significant quadratic term of alcohol use and significant interactions between alcohol use and gender on depressive symptoms. Men with an AUDIT score in the first and fourth quartiles were more likely to report depressive symptoms in comparison to men in the second quartile. Their odds ratios (ORs) and 95% confidence intervals (CIs) were 7.54 (2.00-28.51) and 5.06 (1.31-19.63), respectively. Among women, a linear trend was observed such that those who misused alcohol were three times more likely to have depressive symptoms than those who did not misuse alcohol (OR = 3.03, 95% CI, 1.05-8.80). CONCLUSION: The association between alcohol use and depressive symptoms differed by gender. Additional research is needed to investigate this relationship in Russia. Strategies to reduce alcohol-related problems in Russia may need to consider these differences.

OBJECTIVES: Adenosine signaling has been implicated in the pathophysiology of several psychiatric disorders including alcoholism, depression, and anxiety. Adenosine levels are controlled in part by transport across the cell membrane by equilibrative nucleoside transporters (ENTs). Recent evidence showed that a polymorphism in the gene encoding ENT1 is associated with comorbid depression and alcoholism in women. We have previously shown that deletion of ENT1 reduces ethanol intoxication and elevates alcohol intake in mice. Interestingly, ENT1 null mice display decreased anxiety-like behavior compared to wild-type littermates. However, our behavioral studies were performed only in male mice. Here, we extend our research to include female mice, and test the effect of ENT1 knockout on other behavioral correlates of alcohol drinking, including depressive and compulsive behavior, in mice. METHODS: To assess depression-like behavior, we used a forced swim test modified for mice. We examined anxiety-like behavior and locomotor activity in open field chambers, and perseverant behavior using the marble-burying test. Finally, we investigated alcohol consumption and preference in female mice using a two-bottle choice paradigm. RESULTS: ENT1 null mice of both sexes showed reduced immobility time in the forced swim test and increased time in the center of the open field compared to wild-type littermates. ENT1 null mice of both sexes showed similar locomotor activity levels and habituation to the open field chambers. Female ENT1 null mice displayed increased marble-burying compared to female wild-types, but no genotype difference was evident in males. Female ENT1 null mice showed increased ethanol consumption and preference compared to female wild-types. CONCLUSIONS: Our findings suggest that ENT1 contributes to several important behaviors involved in psychiatric disorders. Inhibition of ENT1 may be beneficial in treating depression and anxiety, while enhancement of ENT1 function may reduce compulsive behavior and drinking, particularly in females.

Extinction of drug-seeking behavior is a form of new and active learning. Facilitation of extinction learning is of clinical interest since cue exposure therapies for the treatment of addiction have largely been unsuccessful in preventing relapse, primarily due to the context specificity of extinction learning. Recently, several studies have shown that potentiation of glutamatergic transmission can facilitate extinction learning in rodent models of cocaine addiction. In this study we investigated the effects of the type 5 metabotropic glutamate receptor (mGluR5) positive allosteric modulator (PAM) 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction and contextual reinstatement of methamphetamine-seeking behavior. Rats were trained and allowed to self-administer methamphetamine (0.1 mg/kg/infusion) in 2 hr daily sessions in Context A where self-administration chambers had distinct tactile, visual, auditory, and olfactory cues. Next, CDPPB (60 mg/kg) or vehicle was administered prior to subsequent extinction training sessions that were conducted in modified self-administration chambers (Context B) that were Context A. Following 16 days of extinction training in Context B, animals were placed back in Context A for assessment of contextual reinstatement of methamphetamine-seeking behavior. CDPPB failed to produce significant reductions in extinction responding or in the magnitude of contextual reinstatement of methamphetamine-seeking compared to vehicle treated controls. We postulate that numerous factors, including methamphetamine-induced changes in mGluR5 receptor expression or function, may have contributed to the observed lack of effects. Although these findings initially suggest that mGluR5 PAMs may be ineffective in facilitating extinction learning or preventing context-induced relapse in methamphetamine addiction, additional studies are warranted examining effects of other mGluR5 PAMs, particularly those with improved pharmacological properties and devoid of potential side effects at higher doses.

Schizophrenia is a severe psychiatric disorder affecting 1% of the world's population. Nicotine addiction is one of the most important health concerns for patients with schizophrenia. An extensive body of evidence points to a high prevalence rate of comorbid nicotine addiction in people with schizophrenia (70-90%), which contributes to significant cardiovascular and cancer risks in this vulnerable population. Therefore, effective smoking cessation strategies could play a major role in preventing significant morbidity and mortality in this population. Two of the most common pharmacological approaches to smoking cessation, bupropion and nicotine replacement therapy (NRT), have been used in psychiatric patients to reduce their smoking. In 2006, varenicline, a partial agonist of α4β2 acetylcholine receptor, was approved for smoking cessation by the FDA. This drug not only has the beneficial effects on withdrawal symptoms, but also reduces craving and rewarding effects of smoking. While varenicline has been shown to be an effective, safe medication for the general population, its efficacy and safety for subjects with schizophrenia is less well characterized. A number of case studies have prompted FDA warnings about the potential exacerbation of psychiatric symptoms. However, other case studies and pilot studies have shown varenicline to be a safe and effective treatment for smoking cessation in subjects with schizophrenia. Varenicline has the potential to reduce smoking in subjects with schizophrenia, however, clinicians should carefully monitor patients receiving varenicline for potential exacerbation of psychiatric symptoms.

Men and women express sexually dimorphic patterns of cocaine abuse, such that women progress faster from initially trying cocaine to becoming dependent upon the drug and display a greater incidence of relapse. Sex differences in response to cocaine are also seen in the laboratory in both humans and animal models. In this review, animal models of cocaine abuse that have reported sex differences in appetitive reinforcement are discussed. In both human and animal studies, sex differences in the subjective and behavioral effects of cocaine are often related to the female reproductive cycle and ovarian hormones. As a comparison, food reinforcement studies have shown the opposite profile of sex differences and the impact of sex steroids on food intake and response rate. In contrast, limited attention has been given to "choice" models in rodents of either sex, however, our recent studies have indicated a role of sex and estrogen in cocaine choice over food with intact females, and OVX females treated with estrogen, choosing cocaine significantly more than males. Interestingly, estrous cycle phase does not seem to impact cocaine choice as it does response rate in single-reinforcer studies, suggesting that genomic rather than neurosteroid effects of estrogen modulate sex differences in this model. Future studies should more fully explore the impact of sex hormones on concurrent reinforcement and discrete choice models of addiction.

Like all other drugs of abuse, the primary therapeutic objective for treating methamphetamine addiction research is the maintenance of abstinence and prevention of relapse to habitual drug-taking. Compounds with the potential to prevent relapse are often investigated in rats that are trained to self-administer intravenous methamphetamine, subjected to extinction training where responding is no longer reinforced, and then given tests for reinstatement of drug-seeking behavior triggered by methamphetamine injections or re-exposure to drug-paired cues. Experimental compounds are administered to the animals prior to the reinstatement tests to evaluate their potential for attenuating or preventing drug-seeking behavior. This article describes the common procedures of the extinction-reinstatement model in studies of this type, and identifies areas of discrepancy. This is followed by a comprehensive overview of the currently published anti-reinstatement effects of pharmacological compounds, classified by the most relevant neurological systems associated with these compounds. The article concludes with a brief discussion of how the study of anti-reinstatement effects can be expanded to further verify existing positive results or to find novel neurobiological targets.

Introduction: Prevalence of hookah or waterpipe smoking is increasing in the United States, particularly among college-aged students. Little research has examined the relationship between hookah smoking, other risk-seeking behaviors, and specific personality factors. The current study aims to address this gap in the literature.

Methods: A random sample of 10,000 students at two southeastern state universities were recruited to complete an online survey containing 230 questions assessing sociodemographics, other substance use, and psychosocial factors. Of students invited to participate, 2,206 (22.1%) returned a completed survey.

Results: Past 30-day hookah use was found among 6.8% (n=141) of the sample. Binary logistic regression indicated that, after controlling for age, ethnicity, and highest parental education, hookah use was associated with being male (p<.001), being a nondaily or daily smoker versus a nonsmoker (p<.001), more frequent alcohol consumption (p<.001), greater sensation seeking (p<.001), lower levels of conscientiousness (p<.001), and greater openness to experiences (p=.01).

Conclusions: Understanding the psychological and personality profiles of hookah users may allow public health practitioners and health care providers to identify high-risk individuals and design targeted interventions addressing users and those at risk for use.

To thrive in any given environment, mobile creatures must be able to learn from the outcomes of both successful and disappointing events. To learn from success, the brain relies on signals originating in the ventral tegmental area and substantia nigra that result in increased release of dopamine in the striatum. Recently, it was shown that to learn from disappointment the brain relies on signals originating in the lateral habenula, which indirectly inhibit dopaminergic activity. The habenula is a small brain region that has been shown in mice to be critical for the appearance of nicotine withdrawal symptoms. The nicotinic acetylcholine receptor subunits expressed in the medial habenula are necessary to observe withdrawal symptoms in mice, and blocking nicotinic activity in the medial habenula only is sufficient to precipitate withdrawal in dependent mice. In addition, recent genome wide association studies have shown that in humans, genetic variants in the same nicotinic receptor subunits are at least partially responsible for the genetic predisposition to become a smoker. The habenula is linked not only to nicotine, but also to the effects of several other drugs. We postulate that the continuous use of drugs of abuse results in habenular hyperactivity as a compensatory mechanism for artificially elevated dopamine release. Drug withdrawal would then result in non-compensated habenular hyperactivity, and could be thought of as a state of continuous disappointment (or a negative emotional state), driving repeated drug use. We believe that drugs that alter habenular activity may be effective therapies against tobacco smoke and drug addiction in general.

To examine the efficacy of a cognitive-behavioral intervention (CBT) to prevent depression among methadone maintenance patients undergoing antiviral treatment for hepatitis C (HCV), 29 patients beginning HCV treatment were randomized to CBT or standard care (SC). Study participants did not meet criteria for major depressive disorder at the time of study recruitment. CBT did not result in less depression-related antiviral treatment failure, better adherence to antiviral treatment, or better HCV RNA outcomes. There were no significant treatment group differences on depressive symptoms over time. The CBT group did display a greater and more consistent decline in both BDI-II and HAM-D scores over time (d=.85 on the BDI-II; d=.72 on the HAM-D).

Tobacco use is a major health problem, and nicotine is the main addictive component. Nicotine binds to nicotinic acetylcholine receptors (nAChR) to produce its initial effects. The nAChRs subtypes are composed of five subunits that can form in numerous combinations with varied functional and pharmacological characteristics. Diverse psychopharmacological effects contribute to the overall process of nicotine addiction, but two general neural systems are emerging as critical for the initiation and maintenance of tobacco use. Mesocorticolimbic circuitry that includes the dopaminergic pathway originating in the ventral tegmental area and projecting to the nucleus accumbens is recognized as vital for reinforcing behaviors during the initiation of nicotine addiction. In this neural system β2, α4, and α6 are the most important nAChR subunits underlying the rewarding aspects of nicotine and nicotine self-administration. On the other hand, the epithalamic habenular complex and the interpeduncular nucleus, which are connected via the fasciculus retroflexus, are critical contributors regulating nicotine dosing and withdrawal symptoms. In this case, the α5 and β4 nAChR subunits have critical roles in combination with other subunits. In both of these neural systems, particular nAChR subtypes have roles that contribute to the overall nicotine addiction process.