Longitudinal investigation of methamphetamine use among gay and bisexual men in New York City: findings from Project BUMPS.
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In recent years, methamphetamine has become a drug more commonly used among gay and bisexual men in New York City. Part of a longitudinal investigation of drug abuse in this population involved assessing the patterns and context of methamphetamine use during the course of 1 year. Findings indicate that among self-identified club-drug-using men, methamphetamine is widely used by men across age groups, educational level, race/ethnicity, and HIV status. Participants reported use of methamphetamine in combination with numerous other illicit and prescribed substances and in a variety of contexts outside the "club scene." Reasons for and contexts of use are related to HIV status, with HIV-positive men indicating a greater likelihood of use to avoid conflict, unpleasant emotions, and social pressures, and reporting higher levels of use in environments such as bathhouses and "sex parties." These patterns and relationships are consistent across time and suggest a complex interaction between person level factors, environmental factors, and HIV. Findings indicate that treatment of methamphetamine addiction among gay and bisexual men must take into account the complex interrelationships between mental health, drug use, sexual risk taking, and HIV. (+info)
Amphetamine-induced effects on neuropeptide Y in the rat brain.
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Repeated (+)-amphetamine sulfate (AMPH) administration (5 mg/kg sc twice daily for 6 days and once on day 7) markedly and reversibly decreased (until 96 h after the final dose) neuropeptide Y-like immunoreactivity (NPY-LI) in the rat striatum (caudate-putamen) and nucleus accumbens, and had no effect on NPY-LI in the hippocampus. No significant alterations were detected in the hybridization signal of NPY mRNA4 and 24 h after the end of AMPH treatment. A single dose of AMPH (5 mg/kg sc) administered to rats 4 and 24 h prior to sacrifice had no effect on NPY-LI in the brain structures studied. Moreover, AMPH injected 8 days after the last dose of repeated AMPH administration did not change NPY-LI up to 72 h. The minimal dose of haloperidol, the strong mixed dopaminergic D2/D1 receptor antagonist, (0.75 mg/kg injected ip 30 min before each of the multiple AMPH administrations) that was sufficient to completely block stereotypy and hyperlocomotion elicited by multiple AMPH administrations enhanced the AMPH-induced decrease in the striatal and accumbens NPY-LI. Our results suggest that NPY neurons in the striatum, nucleus accumbens and hippocampus are not directly involved in the acute behavioral response to AMPH (stereotypy and hyperlocomotion) as well as in the initiation and expression of AMPH-induced behavioral sensitization. (+info)
Patterns of polydrug use among ketamine injectors in New York City.
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Polydrug use is an important public health issue since it has been linked to significant adverse health outcomes. Recently, club drugs, including ketamine and other drugs used in dance/rave scenes, have been identified as key substances in new types of polydrug using patterns. While seemingly a self-explanatory concept, "polydrug" use constitutes multiple drug using practices that may impact upon health risks. Ketamine, a club drug commonly administered intranasally among youth for its disassociative properties, has emerged as a drug increasingly prevalent among a new hidden population of injection drug users (IDUs). Using an ethno-epidemiological methodology, we interviewed 40 young (<25 years old) ketamine injectors in New York during 2000-2002 to describe the potential health risks associated with ketamine and polydrug use. Findings indicate that ketamine was typically injected or sniffed in the context of a polydrug using event. Marijuana, alcohol, PCP, and speed were among the most commonly used drugs during recent ketamine using events. Polydrug using events were often quite variable regarding the sequencing of drug use, the drug combinations consumed, the forms of the drug utilized, and the modes of administrating the drug combinations. Future research should be directed towards developing a more comprehensive description of the risks associated with combining ketamine with other drugs, such as drug overdoses, the transmission of bloodborne pathogens, such as HIV and HCV, the short- and long-term effects of drug combinations on cognitive functioning, and other unanticipated consequences associated with polydrug use. (+info)
Induction of striatal pre- and postsynaptic damage by methamphetamine requires the dopamine receptors.
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Methamphetamine (METH) is a psychostimulant that induces excessive release of dopamine (DA) in the striatum. In this study we have assessed the role of DA D1 and D2 receptors (D1R and D2R) on striatal METH-induced apoptosis and depletion of DA-terminal markers. Male mice were given one i.p. injection of METH (30 mg/kg). Apoptosis was assessed at 24 h, and DA-terminal marker depletion 3 days, after METH. A single toxic dose of METH induced apoptosis in approximately 10-13% of striatal neurons. This was completely prevented by pretreatment (30 min before METH) with either the D1R antagonist SCH-23390 (0.1 mg/kg) or the D2R antagonist raclopride (1 mg/kg). The same dose of METH induced depletion of DA transporter sites up to 61, 56, 71, and 69% in dorsal-medial, ventral-medial, dorsal-lateral, and ventral-lateral striatum, respectively, relative to vehicle-injected controls. Similarly, METH induced depletion of TH protein levels up to 80, 72, 87, and 90% in those respective quadrants. METH induced the expression of glial fibrillary acidic protein throughout the striatum. All these neurochemical changes were significantly attenuated by pretreatment with SCH-23390 (0.1 mg/kg) or raclopride (1 mg/kg). However, pretreatment with either raclopride or SCH-23390 did not prevent METH-induced hyperthermia in mice. These data demonstrate that the induction by METH of both striatal apoptosis and DA-terminal damage requires the activity of the postsynaptic DA receptors in the mouse brain. Moreover, since blockade of either receptor subtype protected from METH, the activity of both DA receptor subtypes is required for the induction of toxicity by METH in the striatum. (+info)
Human methamphetamine pharmacokinetics simulated in the rat: single daily intravenous administration reveals elements of sensitization and tolerance.
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We developed a computer-controlled intravenous methamphetamine (METH) administration procedure (dynamic infusion), which enables us to compensate for an important pharmacokinetic difference between rats and humans by imposing a 12-h half-life for the drug in rats. Dynamic infusion of 0.5 mg/kg METH produced a pharmacokinetic profile that closely simulates the METH exposure pattern in humans, including an apparent half-life of 11.6+/-1.3 h, and an area under the concentration vs time curve of 9.4 microM h, about 20-fold larger than results obtained with typical rat pharmacokinetics. Using this procedure, METH produced a prolonged behavioral stimulation and elevation in caudate extracellular dopamine (DA). Both the behavioral and the DA effects exhibited tolerance to the sustained plasma METH exposure. Single daily dynamic infusion of 0.5 mg/kg METH for 15 days resulted in a progressive enhancement of the behavioral response until about Day 10. On subsequent days, in addition to continued evidence of sensitization, tolerance in the form of a marked decrease in the duration of the behavioral activation became a prominent feature of the response. Qualitative changes in the behavior also emerged. Resumption of METH treatment following 4 days of withdrawal revealed that sensitization was apparent during the first dynamic infusion, and that tolerance re-emerged within two additional days of drug administration. These results showed that a human-like METH exposure pattern produced behavioral and striatal DA response profiles that are both quantitatively and qualitatively different from the effects typically observed with single daily METH injections in rats. Thus, simulation of human METH exposure patterns may be a critical prerequisite to identifying mechanisms relevant to the chronic use of this drug in humans. (+info)
Do preclinical findings of methamphetamine-induced motor abnormalities translate to an observable clinical phenotype?
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This review summarizes the preclinical literature of the effects of methamphetamine (MA) on subcortical dopaminergic and GABAergic mechanisms underlying motor behavior with the goal of elucidating the clinical presentation of human MA-induced movement disorders. Acute and chronic MA exposure in laboratory animal can lead to a variety of motor dysfunctions including increased locomotor activity, stereotypies, diminished or enhanced response times, and parkinsonian-like features. With the exception of psychomotor impairment and hyperkinesia, MA-induced movement disorders are not well documented in humans. This review attempts to draw parallels between the animal and human changes in basal ganglia neurochemistry associated with MA exposure and offers explanations for why a parkinsonian phenotype is not apparent among individuals who use and abuse MA. Significant differences in the expression of neurotoxicity and presence of multiple environmental and pharmacologic confounds may account for the lack of a parkinsonian phenotype in humans despite evidence of altered dopamine function. (+info)
NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice.
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Several lines of evidence support roles for the cell adhesion molecule NrCAM in addictions. Fine mapping within a chromosome 7 region that contains previously linked and associated genomic markers identifies NrCAM haplotypes that are associated with substance abuse vulnerabilities in four samples of abusers and controls. Differential display identifies NrCAM as a drug regulated gene. NrCAM is expressed in neurons linked to reward and memory. NrCAM displays haplotype-specific gene expression in human post-mortem brain samples. Knockout mice display reduced opiate- and stimulant-conditioned place preferences. These observations support NrCAM as a positionally cloned and drug-regulated gene whose variants are likely to change expression and alter substance abuse vulnerabilities in human addictions and animal models of drug reward. (+info)
Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone.
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Repeated intermittent exposure to psychostimulants was found to produce behavioral sensitization. The present study was designed to establish a mouse model and by which to investigate whether opioidergic system plays a role in methamphetamine-induced behavioral sensitization. Mice injected with 2.5 mg/kg of methamphetamine once a day for 7 consecutive days showed behavioral sensitization after challenge with 0.3125 mg/kg of the drug on day 11, whereas mice injected with a lower daily dose (1.25 mg/kg) did not. Mice received daily injections with either 1.25 or 2.5 mg/kg of methamphetamine showed behavioral sensitization after challenge with 1.25 mg/kg of the drug on days 11, 21, and 28. To investigate the role of opioidergic system in the induction and expression of behavioral sensitization, long-acting but non-selective opioid antagonist naltrexone was administrated prior to the daily injections of and challenge with methamphetamine, respectively. Our results show that the expressions of behavioral sensitization were attenuated by pretreatment with 10 or 20 mg/kg of naltrexone either during the induction period or before methamphetamine challenge when they were tested on days 11 and 21. These results indicate that repeated injection with methamphetamine dose-dependently induced behavioral sensitization in mice, and suggest the involvement of opioid receptors in the induction and expression of methamphetamine-induced behavioral sensitization. (+info)