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Drug Addiction (drug + addiction)
Selected AbstractsCREB Gene Transcription Factors: Role in Molecular Mechanisms of Alcohol and Drug AddictionALCOHOLISM, Issue 2 2005Subhash C. Pandey This article presents the proceedings of a symposium presented at the meeting of the Research Society on Alcoholism, held in Vancouver, British Columbia, Canada, in June 2004. The organizers and chairpersons were Subhash C. Pandey and Fulton Crews. The presentations were (1) Ethanol Modulation of CREB: Role in Dependence and Withdrawal, by Fulton Crews; (2) Effects of D1 Dopamine Receptor Activation During Withdrawal From Chronic Morphine: Enhanced CREB Activation and Decreased Conditioned Place Aversion, by Elena H. Chartoff; (3) CREB-Haplodeficient Mice: Role in Anxiety and Alcohol-Drinking Behaviors, by Subhash C. Pandey; and (4) A Role for CREB in Stress and Drug Addiction, by Julie A. Blendy. [source] Drug Interactions between Antiretroviral Medications and Medications Used in the Treatment of Drug Addiction: Research NeedsTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2010Jag H. Khalsa PhD Today substance dependence is one of the major public health problems in the world with millions of people abusing legal and illegal drugs. In addition, almost one-third of the world's population suffers with one or more infections. Both drugs of abuse and infections are associated with serious medical and health consequences, some of which may be exacerbated by the occurrence of pharmacokinetic and/or pharmacodynamic interactions between medications used in the treatment of these conditions when they co-occur. This review briefly discusses issues surrounding clinical management related to drug interactions experienced by substance abusing patients. The emphasis of this paper is on the research needed to further study the extent, nature, and underlying molecular/genetic mechanism(s) of interactions between drugs of abuse, medications used in the treatment of drug addiction, and co-occurring infections.,(Am J Addict 2009;19:96,100) [source] Early adolescents show enhanced acute cocaine-induced locomotor activity in comparison to late adolescent and adult ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2008Kimberly A. Badanich Abstract Initiation of drug use during adolescence is associated with an increased probability to develop a drug addiction. The present study examined dose,response effects of cocaine (0, 5, 10, or 20 mg/kg, i.p.) on locomotor activity in early adolescent (postnatal day (PND) 35), late adolescent (PND 45), and young adults (PND 60) by measuring total distance moved (TDM) and frequency of start,stops. In response to 20 mg/kg cocaine, early adolescents showed the greatest cocaine-induced increase in TDM in comparison to late adolescent and adult rats. At this same dose, early adolescents showed the greatest cocaine-induced attenuation of start,stops relative to older rats. Results suggest that early adolescents engage in more cocaine-induced locomotor activity and less stationary behavior indicating that early adolescents are more sensitive to locomotor activating effects of high dose cocaine than older rats. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 127,133, 2008. [source] ASIA PACIFIC COLUMN: New challenges and opportunities in managing substance abuse in MalaysiaDRUG AND ALCOHOL REVIEW, Issue 5 2006MAHMUD MAZLAN MD Abstract Until recently, Malaysia has lagged behind in the treatment of drug addiction and related disorders, despite experiencing severe drug problems. By the end of 2004, 234 000 heroin users or heroin-dependent individuals had been registered in the official government registry, but other estimates exceed 500 000 for heroin abusers in the country. Amphetamine-type stimulant abuse is also increasing and of considerable public and government concern. Among the population of drug users, HIV and other infectious diseases rates are very high. In the Western Pacific regions, Malaysia has the second highest HIV prevalence (after Vietnam) among adult populations (0.62%) and the highest proportion of HIV cases resulting from injection drug use (76.3%). Drug use and related disorders exert a heavy burden on the country's health care and legal systems. Historically, drug abusers were rehabilitated involuntarily in correctional, rather than health-care, facilities. This primarily criminal treatment approach had limited effectiveness which led to widespread public dissatisfaction and the recent introduction of medical treatments for addiction. Naltrexone was introduced in 1999; buprenorphine was introduced in 2001 and methadone in 2003. Agonist maintenance programmes were embraced rapidly by the medical community in Malaysia. Currently, over 30 000 opiate-dependent patients are treated with agonist maintenance treatments by more than 500 medical practitioners in Malaysia. Despite these recent advances, treatments for amphetamine-type stimulant abuse or dependence are underdeveloped, and diversion of agonist medications is an emerging concern. [source] Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatumADDICTION, Issue 10 2010Sabine Vollstädt-Klein ABSTRACT Aims During the development of drug addiction, initial hedonic effects decrease when substance use becomes habitual and ultimately compulsive. Animal research suggests that these changes are represented by a transition from prefrontal cortical control to subcortical striatal control and within the striatum from ventral to dorsal domains of the striatum, but only limited evidence exists in humans. In this study we address this hypothesis in the context of alcohol dependence. Design, setting and participants Non-abstinent heavy social drinkers (n = 21, 5.0 ± 1.5 drinks/day, 13 of them were alcohol-dependent according to DSM-IV) and light social drinkers (n = 10, 0.4 ± 0.4 drinks/day) were examined. Measurements We used a cue-reactivity functional magnetic resonance imaging (fMRI) design during which pictures of alcoholic beverages and neutral control stimuli were presented. Findings In the dorsal striatum heavy drinkers showed significant higher activations compared to light drinkers, whereas light social drinkers showed higher cue-induced fMRI activations in the ventral striatum and in prefrontal areas compared to heavy social drinkers [region of interest analyses, P < 0.05 false discovery rate (FDR)-corrected]. Correspondingly, ventral striatal activation in heavy drinkers correlated negatively with obsessive-compulsive craving, and furthermore we found a positive association between cue-induced activation in the dorsal striatum and obsessive-compulsive craving in all participants. Conclusions In line with our hypothesis we found higher cue-induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive. [source] Addiction Research Centres and the Nurturing of Creativity The Chinese National Institute on Drug Dependence, Peking University: past, present and futureADDICTION, Issue 9 2010Xi Wang ABSTRACT In the 25 years since drug abuse re-emerged in China in the 1980s, the National Institute of Drug Dependence (NIDD) has made many contributions to China's antidrug campaign. This present paper offers an account of the history, current status and future of drug dependence research at NIDD. NIDD was originally a research centre at Beijing Medical University, founded by the Chinese Ministry of Health to address the rapid spread of drug abuse in China. Originally, the main task of NIDD was to complete the commissions assigned by the government and university. Further developments transformed NIDD into a national research institute in the field of drug addiction that began to conduct its own research. NIDD has now created a professional team spread across several independent departments involved in neurobiological mechanisms, epidemiological surveys and monitoring, pre-clinical and clinical evaluation of new drugs (mainly analgesic drugs and detoxification drugs) and informatics and data analysis. As a university-based research institute, NIDD's funding derives mainly from grants provided by the government and financial support from international organizations. Its past and present research has a gained NIDD a reputation with both practitioners and policy makers in the field of drug addiction. In the future, NIDD will continue to engage in various aspects of drug addiction research and will enter the field of brain function. [source] Puffy hand syndrome due to drug addiction: a case,control study of the pathogenesisADDICTION, Issue 9 2006Valérie Andresz ABSTRACT Aim We studied the pathogenesis of puffy hand syndrome of intravenous drug use. We hypothesized that injections of high-dose sublingual buprenorphine, instead of the recommended sublingual administration, could play an important role in lymphatic obstruction and destruction. Design and participants We set up a case,control study in substitution centres, recruiting intravenous drug addicts with and without puffy hands, respectively. The subjects were asked to answer anonymously a questionnaire of 40 items comprising social and demographic status, history of illicit drugs use, buprenorphine misuse and injection practices. Findings We included 33 cases and 33 controls, mean age of 34 years. They were past heroin users, mainly methadone-substituted. In multivariate analysis, sex (women) (OR = 8.9, P = 0.03), injections in the hands (OR = 5.9, P = 0.03), injections in the feet (OR = 6.5, P = 0.01) and the absence of tourniquet (OR = 7.0, p = 0.02) were significant risk factors for puffy hand syndrome. In 69.7% of the cases and 59.4% of the controls, respectively, there was a high-dose sublingual buprenorphine misuse, although it appeared not to be a significant risk factor for puffy hand syndrome. Conclusions Injection practices are likely to cause puffy hands syndrome, but buprenorphine misuse should not be considered as a significant risk factor. However, intravenous drug users must still be warned of local and systemic complications of intravenous drug misuse. [source] Disability payments, drug use and representative payees: an analysis of the relationshipsADDICTION, Issue 7 2003James A. Swartz ABSTRACT Aims This study attempted to determine: if US federal cash disability payments increase the use of cocaine or opiates among those requalifying for supplemental security income (SSI) disability benefits compared with those who lost benefits; if drug use peaks at the beginning of the month after the receipt of the disability cash disbursement; and if money management by representative payees of requalifying SSI recipients suppresses drug use. Design A multi-site, prospective, 2 year longitudinal design was used with follow-up interviews conducted every 6 months. Urine samples were collected at the final three follow-up interviews. Setting Data were collected in Chicago, IL, Los Angeles, CA, and Seattle, WA, USA. Participants This study used a randomly selected sample of 740 former recipients of SSI who had received disability benefits for drug addiction and alcoholism (DA&A) in 1996, were between the ages of 21 and 59 years, had not received concurrent social security disability insurance and provided testable urine samples and complete self-report data for at least one follow-up interview. Measurements Independent variables included demographics, SSI status at follow-up, representative payee status, drug treatment participation and income. Time of drug testing was operationalized as the first 10 days of the month versus the last 20,21 days based on when the urine sample was collected. The dependent variables were cocaine and opiate use, determined by urinalysis results. Findings Participants were 28% more likely to test positive for cocaine use in the first 10 days of the month than later in the month. This effect was general across all subjects and was not restricted to those receiving SSI benefits. No such effect was found for opiate use. Receiving SSI benefits did not increase cocaine or opiate use generally, nor did having a representative payee suppress use. Conclusions The findings do not support the contentions that federal cash benefits appreciably increase drug use or that representative payees discourage use, at least when use is defined dichotomously. The ,check effect' for cocaine use appears to be general and not confined to those receiving federal cash benefits. The lack of a ,check effect' for opiate use is probably the result of the difference between a relatively steady state of opiate use associated with addiction and a binge pattern of cocaine use triggered by suddenly flush resources. [source] RESEARCH FOCUS ON COMPULSIVE BEHAVIOUR IN ANIMALS: An animal model of compulsive food-taking behaviourADDICTION BIOLOGY, Issue 4 2009Andrea Heyne ABSTRACT The increase in the incidence of obesity and eating disorders has promoted research aimed at understanding the aetiology of abnormal eating behaviours. Apart from metabolic factors, obesity is caused by overeating. Clinical reports have led to the suggestion that some individuals may develop addictive-like behaviours when consuming palatable foods, and compulsive eating plays a similar dominant role in obesity as compulsive drug taking does in drug addiction. The progress made in the development of treatment strategies for obesity is limited, in part, because the physiological and neurological causes and consequences of compulsive eating behaviour are not clearly understood and cannot readily be studied in human subjects. We have developed experimental approaches that reflect the functioning of the components of eating control, including compulsive food taking in rats. Rats that are given free choice between standard chow and a palatable, chocolate-containing ,Cafeteria Diet' (CD) develop distinct signs of compulsive food taking that appear at an early stage. These include the inability to adapt intake behaviour in periods of limited or bitter-tasting CD access, continued food intake during resting phases and changes in fine structure of feeding (duration, distribution and recurrence of feeding bouts). The model will help examine the neurobiological underpinnings of compulsive food seeking and food taking and provides a possibility to study the effects of novel anti-obesity compounds on compulsive eating and other components of food-taking behaviour in detail. For future use of genetic models, the possibility of a transfer to a mouse was discussed. [source] BRIEF REPORT: Varenicline increases striatal dopamine D2/3 receptor binding in ratsADDICTION BIOLOGY, Issue 4 2009Cleo L. Crunelle ABSTRACT Increasing dopamine D2/3 receptor availability is postulated to be a treatment for drug addiction. Varenicline, an ,4,2-nicotinic partial agonist, is effective for nicotine dependence. We hypothesize that varenicline increases dopamine D2/3 receptor availability. Twenty male drug-naïve rats were randomized to varenicline (2 mg/kg) or placebo for 14 days, and then injected with the dopamine D2/3 radiotracer 123I-IBZM. We found significantly higher striatum-to-cerebellum binding ratios in both dorsal and ventral striatum for the varenicline group compared with placebo. Varenicline increases dopamine D2/3 receptor availability in drug-naïve rats. Therefore, varenicline may be an effective treatment for addictions other than smoking. [source] PRECLINICAL STUDY: Amphetamine- and nicotine-induced cross-sensitization in adolescent rats persists until adulthoodADDICTION BIOLOGY, Issue 3 2009Gabriela C. Santos ABSTRACT Nicotine and psychostimulants are often abused in combination and drug abuse often begins during adolescence and can have long-term consequences. Behavioral sensitization has been suggested as an animal model of neuroplasticity implicated in the development of drug addiction. We evaluated whether the pretreatment with nicotine (0.4 mg/kg; s.c.) or amphetamine (5.0 mg/kg; i.p.) in adolescent rats [from postnatal day (P) 28 to P34] could induce cross-sensitization to nicotine and amphetamine when animals were challenged during both adolescence (P37) and adulthood (P70), in separate groups of animals. Adolescent animals pretreated with amphetamine displayed behavioral sensitization to nicotine, which persisted until adulthood. Moreover, adolescent animals pretreated with nicotine showed sensitized locomotor response to amphetamine in the adulthood. These data suggest that adolescents who abuse nicotine may be particularly susceptible to the effects of amphetamine and vice versa. Moreover, this increased vulnerability may persist through their development until adulthood. [source] HEPATITIS C AND ADDICTION: Chronic viral hepatitis is a significant contributor to the immunosenescent phenotype of parenteral drug addictionADDICTION BIOLOGY, Issue 2 2009Albert S. Reece ABSTRACT Intravenous drug addiction is known to be associated with an inordinate morbidity and mortality. As our previous report had identified an immune phenotype consistent with accelerated ageing, we wished to investigate how much of this change may have been related to chronic viral hepatitis. A total of 12 409 clinical pathology results from the period 1995,2007 were reviewed. To control for the differences in age, only patients less than 48 years of age were considered. A total of 636 substance use disorder (SUD) and 6103 non-SUD (N-SUD) patients were studied. They had comparable ages (mean ± SD 31.32 ± 6.90 versus 31.57 ± 9.23, P -value not significant), but the SUD group had more males (74.37% versus 53.20%, P < 0.001). For most of the changes examined splitting the two SUD groups into hepatitis C positive (HCV+) and hepatitis C negative (HCV,) demonstrated that the majority of the described changes were most marked in the HCV+ group. The globulins were higher in the HCV+ group and the albumin was lower and fell more markedly with age than in N-SUD or HCV, (all P < 0.001). The globulin/albumin ratio was significantly higher in HCV+ than HCV, or N-SUD (both P < 0.0001) and rose more with age. These changes were paralleled by the ESR, elevations in the CRP and lymphocyte count. Transaminases were elevated in SUD and HCV+ groups compared with N-SUD (all P < 0.02). At multivariate analysis ESR, lymphocyte count, dual hepatitis B and C seropositivity, AST and HCVAb were significant predictors of the serum globulin level and accounted for 21% of the variance. These data extend our earlier report and show that much of the immunosenescent phenotype of SUD, encompassing the known immunosuppression and the observed immunostimulation, is statistically related to chronic viral hepatitis. Important theoretical and practical management (vaccination) implications ensue. [source] REVIEW: Stress, alcohol and drug interaction: an update of human researchADDICTION BIOLOGY, Issue 1 2009Magdalena Uhart ABSTRACT A challenging question that continues unanswered in the field of addiction is why some individuals are more vulnerable to substance use disorders than others. Numerous risk factors for alcohol and other drugs of abuse, including exposure to various forms of stress, have been identified in clinical studies. However, the neurobiological mechanisms that underlie this relationship remain unclear. Critical neurotransmitters, hormones and neurobiological sites have been recognized, which may provide the substrates that convey individual differences in vulnerability to addiction. With the advent of more sophisticated measures of brain function in humans, such as functional imaging technology, the mechanisms and neural pathways involved in the interactions between drugs of abuse, the mesocorticolimbic dopamine system and stress systems are beginning to be characterized. This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from occasional drug use to drug dependence. We also review factors that contribute to different levels of hormonal/brain stress activation, which has implications for understanding individual vulnerability to drug dependence. Ultimately, these efforts may improve our chances of designing treatment strategies that target addiction at the core of the disorder. [source] Liver transplantation for alcoholic liver diseaseADDICTION BIOLOGY, Issue 4 2001Georges-Philippe Pageaux Although increasing numbers of alcoholic patients are being referred to liver transplant centres, liver transplantation for alcoholic liver disease still remains controversial, essentially because we are in an era of organ shortage. In fact, the main issue is the likelihood of relapse and its influence on outcome, because it is the possibility of returning to alcohol use that separates patients with alcoholic liver disease from those with other forms of chronic liver disease. In all proposed clinical guidelines of indications for referral and assessment for liver transplantation for alcoholic liver disease, the authors emphasize the risk of alcoholism recurrence and, thus, a multidisciplinary approach is required to select patients who are likely to comply with follow-up and not return to a damaging pattern of alcohol consumption after transplantation. It emerges from all clinical studies that when we take into account the usual criteria of success for liver transplantation, i.e. patient and graft survival, rejection rate and infection rate, alcoholic liver disease is a good indication for liver transplantation. Predictive factors for alcoholic relapse after liver transplantation have been assessed in numerous studies, often with contradictory results making these difficult to analyse and compare. Several predictive factors for alcoholic relapse have been studied: length of abstinence before transplantation, associated psychiatric problems, social conditions, associated drug addiction, age. Abstinence after transplantation is the goal, but the necessary treatment for alcoholic disease can result in considerable improvement, even when complete abstinence is not achieved. Finally, the good results obtained with liver transplantation for alcoholic liver disease should help us to educate the general population about alcoholic disease. [source] Decrease of D2 receptor binding but increase in D2 -stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose ,binge' cocaine administration paradigmEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008A. Bailey Abstract Understanding the neurobiology of the transition from initial drug use to excessive drug use has been a challenge in drug addiction. We examined the effect of chronic ,binge' escalating dose cocaine administration, which mimics human compulsive drug use, on behavioural responses and the dopaminergic system of mice and compared it with a chronic steady dose (3 × 15 mg/kg/day) ,binge' cocaine administration paradigm. Male C57BL/6J mice were injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and stereotypy activity were measured and quantitative autoradiographic mapping of D1 and D2 receptors, dopamine transporters and D2 -stimulated [35S]GTP,S binding was performed in the brains of mice treated with this escalating and steady dose paradigm. An initial sensitization to the locomotor effects of cocaine followed by a dose-dependent increase in the duration of the locomotor effect of cocaine was observed in the escalating but not the steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in cocaine-induced stereotypy score was observed from 3 × 20 to 3 × 25 mg/kg/day cocaine. There was a significant decrease in D2 receptor density, but an increase in D2 -stimulated G-protein activity and dopamine transporter density in the striatum of cocaine-treated mice, which was not observed in our steady dose paradigm. Our results document that chronic ,binge' escalating dose cocaine treatment triggers profound behavioural and neurochemical changes in the dopaminergic system, which might underlie the transition from drug use to compulsive drug use associated with addiction, which is a process of escalation. [source] Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigmEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006Jeremy J. Day Abstract Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS,, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS, were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed ,phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS, onset, while the inhibitory subpopulation showed no change in firing during the CS, period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans. [source] Characterization of the mouse adenylyl cyclase type VIII gene promoter: regulation by cAMP and CREBEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2002Jennifer R. Chao Abstract Adenylyl cyclase (AC) type VIII has been implicated in several forms of neural plasticity, including drug addiction and learning and memory. In the present study, we directly examined the role for the transcription factor CREB (cAMP response element binding protein) in regulating ACVIII expression by cloning a 5.2 kilobase region upstream of the translation start site of the mouse ACVIII gene. Analysis of this fragment revealed consensus elements for several transcription factors, including a canonical cAMP response element (CRE) in close proximity to the transcription initiation region. Next, ACVIII promoter activity was studied in two neural-derived cell lines and in primary cultures of rat striatal neurons. Activation of the cAMP pathway by forskolin treatment increased promoter activity, and a series of deletion and point mutants demonstrated that this activation is mediated specifically via the canonical CRE site. Gel shift assays confirmed that this site can bind CREB and several CREB family proteins. Further, activation of the ACVIII promoter by forskolin was potentiated by expression of a constitutively active form of CREB, CREB-VP16, whereas it was inhibited by expression of a dominant-negative form of CREB, A-CREB. Finally, over-expression of CREB in vivo, by viral-mediated gene transfer, induced ACVIII promoter activity in the brains of ACVIII-LacZ transgenic mice. These results suggest that the ACVIII gene is regulated by CREB in vitro and in vivo and that this regulation may contribute to CREB-dependent neural plasticity. [source] Glutamate receptor stimulation induces a persistent rhythmicity of the GABAergic inputs to rat midbrain dopaminergic neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2001Nicola Berretta Abstract The substantia nigra pars compacta and the ventral tegmental area are part of a complex network in the basal ganglia involved in behaviours as diverse as motor planning, generation of pleasure and drug addiction. Here we report that in the dopaminergic neurons of the rat ventral midbrain a brief coactivation of group I metabotropic and NMDA glutamate receptors may transform a temporally dispersed synaptic GABAergic input into a rhythmic pattern (range 4.5,22.5 Hz), probably through a mechanism involving electrotonic couplings. The plastic and long-lasting modification in the temporal code of the inhibitory synaptic activity induced by glutamate may be a key element in determining the function of midbrain dopaminergic neurons in both normal and pathological behaviour. [source] Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophreniaGENES, BRAIN AND BEHAVIOR, Issue 5 2005K. K. Szumlinski Homer proteins are involved in the functional assembly of postsynaptic density proteins at glutamatergic synapses and are implicated in learning, memory and drug addiction. Here, we report that Homer1 -knockout (Homer1 -KO) mice exhibit behavioral and neurochemical abnormalities that are consistent with the animal models of schizophrenia. Relative to wild-type mice, Homer1 -KO mice exhibited deficits in radial arm maze performance, impaired prepulse inhibition, enhanced ,behavioral despair', increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced MK-801- and methamphetamine-stimulated motor behavior. No-net-flux in vivo microdialysis revealed a decrease in extracellular glutamate content in the nucleus accumbens and an increase in the prefrontal cortex. Moreover, in Homer1 -KO mice, cocaine did not stimulate a rise in frontal cortex extracellular glutamate levels, suggesting hypofrontality. These behavioral and neurochemical data derived from Homer1 mutant mice are consistent with the recent association of schizophrenia with a single-nucleotide polymorphism in the Homer1 gene and suggest that the regulation of extracellular levels of glutamate within limbo-corticostriatal structures by Homer1 gene products may be involved in the pathogenesis of this neuropsychiatric disorder. [source] Factors Related to Helicobacter pylori Prevalence in an Adult Population in BrazilHELICOBACTER, Issue 1 2007Schlioma Zaterka Abstract Background:, The prevalence of Helicobacter pylori is higher in developing countries. Sanitary facilities, crowding and ethnic group are some of the factors related to H. pylori infection. The aim of this study was to investigate in blood donors, free of dyspeptic symptoms, the prevalence and factors influencing H. pylori infection. Materials and Methods:, This study was conducted in São Paulo, a city known to have a mixed population coming from all over the country. A total of 1008 blood donors were initially included in the study. After a final revision of all the questionnaires, 993 were included in the final analysis (746 males). H. pylori status was checked by an ELISA test. The following associations to infection were analyzed: sex, age, ethnic group, previous upper gastrointestinal (GI) endoscopy, smoking, alcoholism, drug addiction, type of drinking water, crowding, sanitary facilities, and family income. Results:, Infection was observed in 496 of 746 male (66.5%) and in 156 of 247 female (63.2%) blood donors. Infection prevalence increased according to age group, regardless of sex. Prevalence was lower in White population than in non-White. No relationship was observed between infection and smoking, drug addiction, and alcohol. A positive relation was observed between infection and previous upper GI endoscopy, and type of drinking water, regardless if currently or during childhood. Crowding and lack of toilet in the house during childhood resulted in a higher infection rate. Lower familial income and educational level showed a positive association to infection. Conclusions:, Prevalence of H. pylori is higher in non-White population, independent of gender. A positive association was observed in aging, previous upper GI endoscopy, crowding, type of drinking water, lack of toilet during childhood, lower family income, and lower educational level. [source] Hepatitis C treatment in "difficult-to-treat" psychiatric patients with pegylated interferon-alpha and ribavirin: Response and psychiatric side effects,HEPATOLOGY, Issue 4 2007Martin Schaefer We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric-risk patients and controls with pegylated interferon alpha (pegIFN-,) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders. Seventeen patients without psychiatric diseases or drug addiction (controls), 22 patients with psychiatric disorders, 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN-, plus ribavirin. Sustained virological response (SVR), adherence, and psychiatric side effects (using the Montgomery-Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale) in the groups were compared. An SVR was found in 58.6% of all patients: 58.8% of the controls, 50% of psychiatric patients, 72.2% of methadone patients, and 53.8% of former drug users. Methadone-substituted patients and former drug users had significantly higher dropout rates. Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment. However, the controls had lower pretreatment scores, followed by a significant higher increase to maximum scores. A stepwise logistic regression model showed that only genotype, not group (control, psychiatric, methadone, or former drug abuse), type of psychiatric diagnosis (affective disorder, personality disorder, or schizophrenic disorder), depression scores before and during treatment, change in depression score, antidepressive treatment, sex, or liver enzymes before treatment, was associated with SVR. Conclusion: In an interdisciplinary treatment setting psychiatric diseases and/or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN-, and ribavirin. (HEPATOLOGY 2007.) [source] Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3HISTOPATHOLOGY, Issue 2 2001L Rubbia-Brandt Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3 Aims:,To identify factors associated with liver steatosis in chronic hepatitis C. Methods and results:,Occurrence and severity of liver steatosis in 254 chronic hepatitis C patients were compared with presence of alcohol abuse, body mass index (BMI) >26, history of intravenous drug addiction and hepatitis C virus (HCV) genotype. Steatosis was found in 109 (43%) patients. The occurrence of steatosis was significantly associated with ongoing alcohol abuse (P=0.03) or HCV genotype 3 (P= 0.003), but not with BMI >26. A moderate to severe steatosis was present in 60% of patients infected with HCV genotype 3, irrespective of the presence of alcohol abuse, BMI >26 or history of intravenous drug addiction. Using a multivariable stepwise logistic regression analysis, infection with genotype 3 had an odds ratio (OR) of 10 (95% confidence interval (CI)=4.56,22) for a liver steatosis, whereas the presence of a cirrhosis at histology had an OR=0.256 (95% CI=0.07,0.92). Conclusions:,A moderate to severe degree of steatosis of the liver is a morphological sign suggestive of infection with HCV genotype 3, independent of other risk factors of a fatty liver, but it may disappear at late stages of the disease. [source] Progress towards achieving new vaccine and vaccination goalsINTERNAL MEDICINE JOURNAL, Issue 7 2003G. Ada Abstract Viral and bacterial vaccines, especially for childhood use, are one of the most successful public health measures of the last two centuries and have a good safety record. However, there are still many diseases that are caused by infectious agents for which vaccines are not available. Our increasing ability to manipulate the immune system offers hope that, in the future, at least some of these infections may be prevented by vaccination. A surprising recent development is the use of vaccine technology to test whether a range of other generally non-communicable diseases can be prevented (or at least controlled) in this way. Investigation of these diseases is still mainly at the experimental level, however the list includes different types of cancers, allergies, drug addiction and neurodegenerative diseases. (Intern Med J 2003; 33: 297,304) [source] Could a common biochemical mechanism underlie addictions?JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2000C. Betz The subject of ,drug addiction' is multifaceted and many aspects of it (even some of the definitions) are controversial. Collateral medical problems include the spread of HIV and hepatitis C virus secondary to i.v. drug abuse and effects on prenatal brain development ( 1). Progress in the understanding of the causes of addictions and its treatment has been impeded by the lack of a unifying biochemical theory. However, recent evidence suggests that some common mechanism might underlie addictions to otherwise apparently unrelated drugs. A major hypothesis has emerged suggesting that the neurotransmitter dopamine (DA) might play a central role in the molecular mechanisms of at least some addictions. If so, it would represent an important target for discovery of effective pharmacotherapy and revolutionize the pharmacist's role in treating addictions. This short overview outlines the status of the theory of a common biochemical mechanism of drug addiction. [source] A synergy between action-research and a mixed methods design for improving services and treatment for family members of heavy alcohol and drug usersJOURNAL OF COMMUNITY & APPLIED SOCIAL PSYCHOLOGY, Issue 2 2010Caterina Arcidiacono Abstract Our project first explored the patterns of disempowerment within 113 Italian families facing the problem of a heavy alcohol or drug user in the family. It then provided therapeutic interventions for the members of a further fifty-two families, and thirdly, as a part of the diffusion of the results, it provided brief training for 1,011 professionals supplying services for those suffering from alcohol and drug addiction. Research undertaken in the UK, Mexico and Australia (Copello, Templeton, & Velleman, 2006; Orford et al., 2005a; Orford, Templeton, Velleman, & Copello, 2005b; Velleman & Templeton, 2003) on the impact of substance misuse on families, and on the development of effective interventions to assist those families, supplied the models for this participatory research in Italy. This article discusses the mobilization of health professionals in developing a participatory project within a cross-cultural framework, focusing on research that involved more than 70 researchers and other professionals all over Italy. Research team discussions, peer validation of gathered data and reflexivity all had a significant role. The paper illustrates various issues, which are often not explicitly mentioned in research reports, related to recruitment, cooperation between researchers, interactions between researchers and participants, information about decision-making and the actual modalities of execution of the project. Moreover, the careful descriptions of qualitative research principles within the action research approach and a mixed methods design should enhance the research competencies of psychologists and social scientists involved in the community. Copyright © 2009 John Wiley & Sons, Ltd. [source] Striatal regulation of ,FosB, FosB, and cFos during cocaine self-administration and withdrawalJOURNAL OF NEUROCHEMISTRY, Issue 1 2010Erin B. Larson J. Neurochem. (2010) 115, 112,122. Abstract Chronic drug exposure induces alterations in gene expression profiles that are thought to underlie the development of drug addiction. The present study examined regulation of the Fos-family of transcription factors, specifically cFos, FosB, and ,FosB, in striatal subregions during and after chronic intravenous cocaine administration in self-administering and yoked rats. We found that cFos, FosB, and ,FosB exhibit regionally and temporally distinct expression patterns, with greater accumulation of ,FosB protein in the nucleus accumbens (NAc) shell and core after chronic cocaine administration, whereas ,FosB increases in the caudate-putamen (CPu) remained similar with either acute or chronic administration. In contrast, tolerance developed to cocaine-induced mRNA for ,FosB in all three striatal subregions with chronic administration. Tolerance also developed to FosB expression, most notably in the NAc shell and CPu. Interestingly, tolerance to cocaine-induced cFos induction was dependent on volitional control of cocaine intake in ventral but not dorsal striatal regions, whereas regulation of FosB and ,FosB was similar in cocaine self-administering and yoked animals. Thus, ,FosB-mediated neuroadaptations in the CPu may occur earlier than previously thought with the initiation of intravenous cocaine use and, together with greater accumulation of ,FosB in the NAc, could contribute to addiction-related increases in cocaine-seeking behavior. [source] Dopamine D1 and D3 receptors oppositely regulate NMDA- and cocaine-induced MAPK signaling via NMDA receptor phosphorylationJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Hongyuan Jiao Abstract Development of drug addiction involves complex molecular changes in the CNS. The mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in mediating neuronal activation induced by dopamine, glutamate, and drugs of abuse. We previously showed that dopamine D1 and D3 receptors play different roles in regulating cocaine-induced MAPK activation. Although there are functional and physical interactions between dopamine and glutamate receptors, little is known regarding the involvement of D1 and D3 receptors in modulating glutamate-induced MAPK activation and underlying mechanisms. In this study, we show that D1 and D3 receptors play opposite roles in regulating N -methyl- d -aspartate (NMDA) -induced activation of extracellular signal-regulated kinase (ERK) in the caudate putamen (CPu). D3 receptors also inhibit NMDA-induced activation of the c-Jun N-terminal kinase and p38 kinase in the CPu. NMDA-induced activation of the NMDA-receptor R1 subunit (NR1), Ca2+/calmodulin-dependent protein kinase II and the cAMP-response element binding protein (CREB), and cocaine-induced CREB activation in the CPu are also oppositely regulated by dopamine D1 and D3 receptors. Finally, the blockade of NMDA-receptor reduces cocaine-induced ERK activation, and inhibits phosphorylation of NR1, Ca2+/calmodulin-dependent protein kinase II, and CREB, while inhibiting ERK activation attenuates cocaine-induced CREB phosphorylation in the CPu. These results suggest that dopamine D1 and D3 receptors oppositely regulate NMDA- and cocaine-induced MAPK signaling via phosphorylation of NR1. [source] Androgen Decreases Dopamine Neurone Survival in Rat MidbrainJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2010M. L. Johnson Clinical studies show that men are more likely to develop disorders affecting midbrain dopaminergic pathways, such as drug addiction and Parkinson's disease (PD). Although a great deal of focus has been given to the role of oestrogen in the maintenance of midbrain dopaminergic pathways, little is known about how testosterone influences these pathways. In the present study, we used stereological analysis of tyrosine hydroxylase-immunoreactive (TH-IR) cell bodies to determine how testosterone influences the dopaminergic cell bodies of the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Rats and mice were castrated at postnatal day (PN) 60, and these midbrain cell populations were counted on PN 90. One month after castration, TH-IR cell number had increased in the SNpc and VTA of rats and mice. Replacement with testosterone or the non-aromatisable analogue dihydrotestosterone (DHT) in castrated animals reduced TH-IR cell number in the SNpc and VTA in rats. In mice, the decrease of TH-IR cell number with testosterone or DHT replacement was observed only in the SNpc. The apparent increase in TH-IR neurone number after castration is not explained by an increase in TH expression because the number of nondopaminergic cells (TH-immunonegative, TH-IN) did not decrease proportionally after castration. TH-IN cell number did not change after castration or hormone replacement in rat or mouse SNpc or VTA. These findings suggest that testosterone may play a suppressive role in midbrain dopaminergic pathways. [source] Alcohol Inhibits Spontaneous Activity of Basolateral Amygdala Projection Neurons in the Rat: Involvement of the Endocannabinoid SystemALCOHOLISM, Issue 3 2008Simona Perra Background:, A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol. Methods:, We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens. Results:, Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 ± 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 ± 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose,response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 ± 16% of baseline firing at 0.5 g/kg, p < 0.05). Conclusions:, Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism. [source] The European NEAT Program: An Integrated Approach Using Acamprosate and Psychosocial Support for the Prevention of Relapse in Alcohol-Dependent Patients With a Statistical Modeling of Therapy Success PredictionALCOHOLISM, Issue 10 2002Isidore Pelc Background A multicenter, prospective study was conducted in five European countries to observe outcome in alcohol misusers treated for 24 weeks with acamprosate and various psychosocial support techniques, within the setting of standard patient care. Methods Patients diagnosed as alcohol dependent using DSM-III-R criteria were treated, for 24 weeks, with acamprosate and appropriate psychosocial support. Potential predictor variables were recorded at inclusion. Drinking behavior was monitored throughout; the proportion of cumulative abstinence days was the principal outcome measure. The influence of baseline clinical and demographic variables on outcome was assessed using multiple regression analysis. Adverse events were recorded systematically. Results A total of 1289 patients were recruited; 1230 took at least one dose of the drug and provided at least one set of follow-up data; 543 (42.1%)patients were observed for the full 24-week period. The overall proportion of cumulative abstinence days was 0.48. Multiple physical and psychiatric comorbidities and a history of drug addiction were negatively correlated with outcome, as were, to a lesser extent, multiple previous episodes of detoxification, unemployment, and living alone. Older age and stable employment were positively associated with outcome. The difference in the unadjusted proportion of cumulative abstinence days between countries was significant (p < 0.001) but less so when adjusted for the predictive factors identified in the multivariate model (p < 0.019). Overall, outcome was not influenced by the nature of the psychosocial support provided. Adverse events were generally mild, with gastrointestinal disorders, which occurred in 21.5% of patients, being the most frequent. Conclusions This open-label study confirms the efficacy and safety of acamprosate in the treatment of alcohol dependence in the setting of standard patient care. Treatment benefit was observed irrespective of the nature of the psychosocial support provided. Predictors of the response to treatment were identified; their heterogeneous distribution within the study population explained, at least in part, the differences in outcome between countries. [source] | ||||||||||||||||||||||