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At least 19 recordsLinked to original sources

Conditioned learning in young rats born of drug-addicted parents and raised on addictive drugs.

Ratlings born of six drug-addicted and a control group of parent rats were raised under the influence of the same drugs administered in drinking water. They were trained in a conditioned avoidance paradigm (CAR) from the 7th week when the drugs were withdrawn except in two subgroups of flurazepam and morphine. The growth rate was not appreciably impaired except for temporary slowness in morphine and alcohol-raised rats; it was faster in phenobarbitone and meprobamate-raised rats. The CAR-acquisition rates of the treatment groups were quite close and parallel to that of the controls except for the morphine, meprobamate, medazepam and the two drug-trained subgroups; whereas, the rats raised on low-dose morphine showed a faster than control acquisition rate. No evidence of state-dependent learning was obtained from this study.

Animals↗

[Biological addictive drugs--is there a change in drug taking behavior of young drug addicts?].

Abuse of natural products was frequently noticed among young patients with multiple substance abuse. 180 patients of a rehabilitation clinic for young addicts filled out a questionnaire regarding their regularly consumed drugs. Ayahuasca and cactus, the natural drugs of the 70's are rarely found. The patients frequently consumed psilocybin, amanita and datura. We inform about the toxicological basis of the used drugs. A specific exploration of patients with multiple substance abuse in regard to the use of biological drugs is an necessary as random and multicentre follow-up-studies.

Adult↗

Immune response to hepatitis B vaccine in drug addicts.

Drug addicts are at high risk of hepatitis B infection and are therefore candidates for vaccination against hepatitis B. Since drug addicts may have an impaired immune response, and low compliance for therapy extending over several months, we evaluated a vaccination scheme according to the instruction of the manufacturer (HB- Vax 20 micrograms at zero, one and six months) in drug addicts using daily methadone (Group M), in drug addicts in residential detoxification programmes (Group D), and in treatment centre staff who were seronegative for hepatitis Bs (Group S). All 23 controls and 20 of 21 of Group D completed the vaccination programme, in contrast to 14 of 24 in Group M. Anti-HBs developed in 91 per cent of Group S and in all addicts tested at six months. Anti-HBs titres at seven months were higher than 100 RIA units in 55 per cent of Group S, in 94 per cent of Group D and in 44 per cent of Group M. We conclude that HB- Vax induces production of anti-HBs equally well in drug addicts and in controls: a shorter-duration vaccination schedule might be more appropriate for 'non-captive' drug addicts living outside therapeutic communities.

Hepatitis B↗

[Current clinical aspects of drug addiction].

Drug addiction is a serious behavioral disorder. It is a long term evolving process characterized by dependency. It is not only biological and psychological but also social. It should be differentiated from occasional drug use, from drug abuse with minor consequences as well from medical drug dependency in which the individual does not seek a psychological effect. Drug addiction causes are multiple and include psychological, family, social and obviously biological factors (drug addicting potential). In to-day clinical practice, addiction to benzodiazepines or opioids prescribed for maintenance therapy and the newly described secondary addiction of later onset are predominant. Severe social consequences and many psychiatric and medical disorders in particular due to HIV infection also result from drug addiction. Depressive and psychotic disorders cause specific therapeutic problems when patients deny their troubles or when drug use produces special relief. These psychological disorders frequently underlie medical care needs.

Adolescent↗

Neural substrates of drug craving and relapse in drug addiction.

Drug addiction is characterized by motivational disturbances such as compulsive drug taking and episodes of intense drug craving. Recent advances using animal models of relapse have shown that drug-seeking behaviour can be triggered by drug-associated cues, by stress and by 'priming' injections of the drugs themselves, events also known to trigger drug craving in human drug addicts. Current evidence suggests that these stimuli all induce relapse, at least in part, by their common ability to activate the mesolimbic dopamine system. Drug-associated cues and stress can activate this system via neural circuits from the prefrontal cortex and amygdala and through activation of the hypothalamic-pituitary-adrenal axis. Our studies suggest that dopamine triggers relapse to drug-seeking behaviour by stimulating D2-dopamine receptors which inhibit the cyclic AMP second messenger pathway in the neurones of the nucleus accumbens. In contrast, compounds which activate D1 receptors prevent relapse to drug-seeking behaviour, possibly through satiation of reward pathways. Chronic neuroadaptations in dopamine receptor signalling pathways in the nucleus accumbens caused by repeated drug use are hypothesized to produce tolerance to the rewarding effects of D1-receptor stimulation, leading to increased drug intake during drug self-administration. Conversely, these same neuroadaptations are hypothesized to enhance drug craving by potentiating D2 receptor-mediated signals during abstinence. These findings identify D1 and D2-dopamine receptor mechanisms as potential targets for developing anticraving compounds to treat drug addiction.

Animals↗

Molecular genetic probing of dopamine receptors in drug addiction.

Drug addiction is a brain disease with complex genetic, psychological and social factors. The dopaminergic system of the brain plays a central role in natural reward and motivation and is the main neural substrate for the actions of abusive drugs. The analysis of mice with mutations in their dopamine receptor genes has provided new information regarding the influence of individual dopamine receptors on drug actions. The use of genetic manipulation of dopamine receptors, and related intracellular signaling molecules, in mice will help to enhance our understanding of the molecular and cellular mechanisms underlying compulsive drug-seeking and drug-taking behaviors, reasons for relapse into drug addiction and persistent neuronal changes in response to repeated drug use. These studies will provide new insights for improved therapeutic strategies for the prevention and treatment of drug addiction.

Animals↗

Methadone and drug addicts.

Drug addicts who had died in Copenhagen City and County in 1981 and 1989 were analysed for methadone. In 1981, 94 cases were analysed of which 16% were found positive for methadone, and in 1989, 70 cases were analysed of which 37% were positive. Methadone alone was found to be the cause of death in 50% more cases in 1989 than in 1981. Only half of the drug addicts who were found positive for methadone had been under methadone treatment. Morphine and benzodiazepines were the most frequently occurring other substances in both 1981 and 1989. Alcohol was found in only about 30% of the methadone-positive cases. The median whole blood concentrations of methadone found in addicts where methadone was the cause of death was 0.3 mg/kg where no alcohol was present and 0.2 mg/kg where alcohol was present. In living persons using methadone, the median was 0.1 mg methadone/kg whole blood with or without alcohol present.

Adolescent↗

Limbic-striatal memory systems and drug addiction.

Drug addiction can be understood as a pathological subversion of normal brain learning and memory processes strengthened by the motivational impact of drug-associated stimuli, leading to the establishment of compulsive drug-seeking habits. Such habits evolve through a cascade of complex associative processes with Pavlovian and instrumental components that may depend on the integration and coordination of output from several somewhat independent neural systems of learning and memory, each contributing to behavioral performance. Data are reviewed that help to define the influences of conditioned Pavlovian stimuli on goal-directed behavior via sign-tracking, motivational arousal, and conditioned reinforcement. Such influences are mediated via defined corticolimbic-striatal systems converging on the ventral striatum and driving habit-based learning that may depend on the dorsal striatum. These systems include separate and overlapping influences from the amygdala, hippocampus, and cingulate and medial prefrontal cortex on drug-seeking as well as drug-taking behavior, including the propensity to relapse.

Conditioning, Psychological↗

Response to HBV vaccine in relation to anti-HCV and anti-HBc positivity: a study in intravenous drug addicts.

Drug addicts represent the group of young adults with the lowest response to hepatitis B virus (HBV) vaccine. A study was carried out on 110 current intravenous heroin users attending the service providing assistance to intravenous drug users (IVDUs) (SERT) in Padua: 66.4% of them were found anti-hepatitis C virus (HCV)-positive and 33.6% were anti-HBc positive; 29.9% were positive for both. The subjects were vaccinated with 10 microg of yeast-derived vaccine at months 0, 1 and 2 (fast schedule). The overall response rate was 66.4%. Response seems to be affected by positivity to anti-HBc, but not to HCV infection.

Adult↗

Combining research approaches to advance our understanding of drug addiction.

Drug addiction is a complex behavior, likely to be influenced by various genes, environmental factors, and gene-gene and gene-environment interactions. Various aspects of addiction are studied by different disciplines. Animal studies are increasing insight into brain regions and genes associated with addiction. Epidemiologic studies are establishing the factors increasing risk for initiation and continuation of substance use. Twin and adoption studies are increasing our understanding of the complex mechanisms involved in substance use, including comorbidity and gene environment interaction. Finally, molecular genetic studies in humans are starting to yield some converging findings. It is argued and illustrated with examples that greater awareness of progress in other disciplines can speed up our understanding of the complex processes involved in addiction. This should help our ability to identify who is at increased risk of becoming addicted and the development of prevention and intervention strategies targeted at an individual's specific needs.

Adolescent↗

Plasticity of reward neurocircuitry and the 'dark side' of drug addiction.

Drug seeking is associated with activation of reward neural circuitry. Here we argue that drug addiction also involves a 'dark side'--a decrease in the function of normal reward-related neurocircuitry and persistent recruitment of anti-reward systems. Understanding the neuroplasticity of the dark side of this circuitry is the key to understanding vulnerability to addiction.

Animals↗

Behavioural adaptations to addictive drugs in mice lacking the NMDA receptor epsilon1 subunit.

N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptors (GluRs) formed by assembly of the GluRzeta subunit (called NR1 in rats) with any one of four GluRepsilon subunits (GluRepsilon1-4; NR2A-D), play an important role in excitatory neurotransmission, synaptic plasticity and brain development. Recent pharmacological studies have also indicated a role for NMDA receptors in drug addiction. In the present study, we investigated the behavioural adaptations to addictive drugs such as phencyclidine (PCP), methamphetamine (MAP) and morphine (MOR) in mice lacking the GluRepsilon1 subunit of the NMDA receptor. GluRepsilon1 mutant mice exhibited a malfunction of NMDA receptors, as evidenced by the reduction of [3H]MK-801 binding in an autoradiographic receptor binding assay. GluRepsilon1 mutant mice showed an attenuation of acute PCP- and MAP-induced hyperlocomotion. The development of sensitization by repeated treatment with PCP and MAP at a low, but not high, dose was also suppressed. The development of MOR-induced analgesic tolerance and naloxone-precipitated MOR withdrawal symptoms were attenuated in GluRepsilon1 mutant mice. In the place conditioning test, PCP-induced place aversion in naive mice and place preference in PCP-pretreated mice, as well as MOR-induced place preference, were diminished whereas MAP-induced place preference was not affected in GluRepsilon1 mutant mice. These findings provide genetic evidence that GluRepsilon1 subunit-containing NMDA receptors are involved in certain aspects of drug addiction.

Adaptation, Physiological↗

Dopamine and drug addiction: the nucleus accumbens shell connection.

Microdialysis studies in animals have shown that addictive drugs preferentially increase extracellular dopamine (DA) in the n. accumbens (NAc). Brain imaging studies, while extending these finding to humans, have shown a correlation between psychostimulant-induced increase of extracellular DA in the striatum and self-reported measures of liking and 'high' (euphoria). Although a correlate of drug reward independent from associative learning and performance is difficult to obtain in animals, conditioned taste avoidance (CTA) might meet these requirements. Addictive drugs induce CTA to saccharin most likely as a result of anticipatory contrast of saccharin over drug reward. Consistently with a role of DA in drug reward, D2 or combined D1/D2 receptor blockade abolishes cocaine, amphetamine and nicotine CTA. Intracranial self-administration studies with mixtures of D1 and D2 receptor agonists point to the NAc shell as the critical site of DA reward. NAc shell DA acting on D1 receptors is also involved in Pavlovian learning through pre-trial and post-trial consolidation mechanisms and in the utilization of spatial short-term memory for goal-directed behavior. Stimulation of NAc shell DA transmission by addictive drugs is shared by a natural reward like food but lacks its adaptive properties (habituation and inhibition by predictive stimuli). These peculiarities of drug-induced stimulation of DA transmission in the NAc shell result in striking differences in the impact of drug-conditioned stimuli on DA transmission. It is speculated that drug addiction results from the impact exerted on behavior by the abnormal DA stimulant properties acquired by drug-conditioned stimuli as a result of their association with addictive drugs.

Animals↗

[Nicotine--drug addiction--AIDS. Drug use habits of Vienna addicts].

In Austria it is illegal to sell tobacco to young adolescents. A diverse sample of 358 narcotic addicts was investigated at the Psychiatric University Clinic of Vienna. Data were obtained from on site confidential interviews and a HIV-test was conducted. The individual drug use history was recorded and, interestingly, tobacco addiction was the first stage in starting a drug career. Furthermore, a strong correlation was observed between onset of heroin use and HIV-1 infection. It is concluded that in Austria not only the availability nicotine and alcohol to young adolescents should be prohibited, but also their use should be punishable. Easy access to nicotine as in public restaurants or from automatic distributors, has to be withdrawn. Tobacco advertisements may drive vulnerable young adolescents to early nicotine abuse and this may be followed by addition to other drugs and diseases causing death, including AIDS. Socioeconomic data, as well as the methadone data are presented. 180 out of the 358 patients were on methadone maintenance. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society. Physicians have a clear responsibility to lead the effort on all fronts against tobacco, especially in view of the HIV epidemic.

Adolescent↗

[Infections and other causes of mortality correlated with drug addiction].

Drug use and related injection practices determine an excess mortality in drug abusers compared to the general population adjusted for age and gender. HIV/AIDS and overdose are the most important causes of death among injecting drug users; however, excess mortality is also due to other causes, such as cirrhosis and endocarditis. Infections have a great impact on the health of injection drug users. Viral infections, such as HIV, HCV, and HBV, are the most important ones, but bacterial and fungal infections, and, to a lesser extent, protozoal infections, are also common. In depth knowledge of drug-related morbidity and mortality causes is important to improve clinical skills and to implement control activities.

Cause of Death↗