Melatonin attenuates methamphetamine‐induced overexpression of pro‐inflammatory cytokines in microglial cell lines

Abstract: Methamphetamine (METH), the most commonly abused drug, has long been known to induce neurotoxicity. METH causes oxidative stress and inflammation, as well as the overproduction of both reactive oxygen species (ROS) and reactive nitrogen species (RNS). The role of METH‐induced brain inflammation remains unclear. Imbroglio activation contributes to the neuronal damage that accompanies injury, disease and inflammation. METH may activate microglia to produce neuroinflammatory molecules. In highly aggressively proliferating immortalized (HAPI) cells, a rat microglial cell line, METH reduced cell viability in a concentration‐ and time‐dependent manner and initiated the expression of interleukin 1β (IL‐1β), interleukin 6 (IL‐6) and tumor necrosis factor α. METH also induced the production of both ROS and RNS in microglial cells. Pretreatment with melatonin, a major secretory product of the pineal gland, abolished METH‐induced toxicity, suppressed ROS and RNS formation and also had an inhibitory effect on cytotoxic factor gene expression. The expression of cytotoxic factors produced by microglia may contribute to central nervous system degeneration in amphetamine abusers. Melatonin attenuates METH toxicity and inhibits the expression of cytotoxic factor genes associated with ROS and RNS neutralization in HAPI microglia. Thus, melatonin might be one of the neuroprotective agents induced by METH toxicity and/or other immunogens.     

Beneficial effects of Tai Chi for amphetamine-type stimulant dependence: a pilot study

ABSTRACT

Background: Tai Chi is a traditional Chinese sport that is classified as a moderate exercise. Recent studies have evaluated the effectiveness of Tai Chi in substance abuse rehabilitation. Objectives: The aim of this study was to assess the quality of life and physical effects of a Tai Chi intervention on individuals with amphetamine-type stimulant (stimulant) dependence. Methods: Sixty male subjects with stimulant dependence from a Shanghai Mandatory Detoxification and Rehabilitation Center participated in a 12-week trial. Tai Chi was used as an intervention in the experimental group (n = 30). The control group (n = 29) underwent standard care, which included recreation activity, gesture language exercise, and self-education. Outcome measures included the quality of life for drug addiction (QOL-DA) questionnaire [four scales consisting of physiology (e.g., energy level), psychology (e.g., depression), symptoms (e.g., physical symptoms), society (e.g., interpersonal) and fitness evaluations (assessed by body mass index, body fat, hand-grip, flexibility, balance)]. Repeated measures were used to analyze the changes over time. Results: Test scores of the QOL-DA in the Tai Chi group significantly increased after 12 weeks in the following areas: physiology, 8.71 (p = 0.005), symptoms, 4.34 (p = 0.042), society, 15.79 (p < 0.001), and total score, 10.60 (p = 0.002). A post hoc test further revealed that quality of life improved in the Tai Chi group but not in the standard care group. Physical results showed a significant interaction with balance(F_(1,56) = 6.92, p = 0.011); participants in the Tai Chi group improved by 10 s while there was no change in the standard care group. Although there were no significant interactions in the fitness outcomes (i.e., hand-grip and sit-and-reach tests), the within-group factor displayed significant changes in body fat (F_(1,56) = 27.79, p < 0.001) in both groups. Conclusion: This study demonstrates that Tai Chi is a promising exercise that improves quality of life for individuals with stimulant dependence.     

Withdrawal symptoms in abstinent methamphetamine‐dependent subjects

Aims Withdrawal symptoms have been linked to a propensity for relapse to drug abuse. Inasmuch as this association applies to methamphetamine (MA) abuse, an understanding of the course of MA withdrawal symptoms may help to direct treatment for MA dependence. Previous studies of symptoms manifested during abstinence from MA have been limited in size and scope. We asked (i) whether debilitating psychological and/or physical symptoms appear during the first several weeks of MA abstinence, (ii) how craving for MA evolves and (iii) whether psychiatric symptoms (e.g. depression, psychosis) persist beyond a month of abstinence. Design A study of MA‐dependent participants, who initiated and maintained abstinence from the drug for up to 5 weeks, compared to a matched healthy comparison group. Setting In‐patient research hospital ward (MA‐dependent subjects) and out‐patient (comparison subjects). Participants Fifty‐six MA‐dependent and eighty‐nine comparison subjects. Measurements Rater‐assessed MA withdrawal questionnaire and self‐report assessment of craving (MA‐dependent subjects) and self‐report assessment of psychiatric symptoms (both groups). Findings At study entry, MA‐dependent subjects exhibited a wide range in severity of depressive symptoms, with the average score at a mild–moderate level of severity. Symptoms of psychosis were also prevalent. While depressive and psychotic symptoms largely resolved within a week of abstinence, craving did not decrease significantly from the time of initiating abstinence until the second week, and then continued at a reduced level to the fifth week. Conclusions Depressive and psychotic symptoms accompany acute withdrawal from methamphetamine but resolve within 1 week. Craving is also present and lasts at least 5 weeks.     

Modulation of the Proteome of Peripheral Blood Mononuclear Cells from HIV-1-Infected Patients by Drugs of Abuse

Introduction  We used proteomic analyses to assess how drug abuse modulates immunologic responses to infections with the human immunodeficiency virus type 1 (HIV-1). Methods  Two-dimensional difference gel electrophoresis was utilized to determine changes in the proteome of peripheral blood mononuclear cells (PBMC) isolated from HIV-1-positive donors that occurred after treatment with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins. We further isolated specific subpopulations of PBMC to determine which subpopulations were selectively affected by treatment with drugs of abuse. Monocytes, B cells, and T cells were positively or negatively selected from PBMC isolated from HIV-1-positive donors. Results  Our results demonstrate that cocaine and methamphetamine modulate gene expression primarily in monocytes and T cells, the primary targets of HIV-1 infection. Proteomic data were validated with quantitative, real-time polymerase chain reaction. These studies elucidate the molecular mechanisms underlying the effects of drugs of abuse on HIV-1 infections. Several functionally relevant classes of proteins were identified as potential mediators of HIV-1 pathogenesis and disease progression associated with drug abuse.     

Antagonism of footshock stress-induced inhibition of intracranial self-stimulation by naloxone or methamphetamine

Rats were trained to lever-press for intracranial self-stimulation (ICSS) with electrodes implanted in the ventral tegmental area (VTA). The effect of inescapable footshock on response rates to ICSS was examined in the present study. Markedly decreased response rates to ICSS were observed 15 min to 24 h following inescapable footshock. Naloxone (10.0 mg/kg) itself was without effect on response rates to ICSS, but completely antagonized the decreased response rates by the stressor treatment. A relatively low dose of methamphetamine (0.5 mg/kg), which showed no effect on ICSS rates in naive rats, also antagonized the decreased response rates to ICSS. The present results suggest that inescapable footshock may release endorphin in the mesolimbic or mesocortical area; the released endorphin may act on dopaminergic nerve endings and interrupt dopaminergic transmission. The decreased activity of dopaminergic neurons may cause the decreased response rates to ICSS.     

One-year follow-up after multimodal inpatient treatment for cocaine and methamphetamine dependecies

Of a randomly selected sample of 214 patients treated with aversion therapy for cocaine dependence in four chemical dependency units operated by Schick Shadel Hospitals, 156 were followed up 12 to 20 months posttreatment (average 15.2 months). Significant other validation was obtained in 33%. Total abstinence from cocaine for the group overall was 53% at one year post treatment, and current abstinence of at least 6 months at follow-up was 68.6%. Those treating with aversion for cocaine alone had a one-year abstinence of 39% and a current abstinence of 62.4%. Those treating with aversion for alcohol and cocaine had a one-year total abstinence from cocaine of 69% and a current abstinence of 76%. Those treating with aversion for cocaine and marijuana had a one-year total abstinence from cocaine of 50% and a current abstinence of 65%. Those treating with aversion for alcohol, cocaine, and marijuana had a one-year total abstinence from cocaine of 73% and a current abstinence of 73%. One-year total abstinence from alcohol was 54% for those receiving aversion for both alcohol and cocaine and 77% for those receiving aversion for alcohol, cocaine, and marijuana. Current abstinence from alcohol at follow-up was 68% and 81%, respectively. One-year total abstinence from marijuana was 42% for those treating with aversion for cocaine One-year total abstinence from marijuana was 42% for those treating with aversion for cocaine and marijuana and 64% for those treating with aversion for alcohol, cocaine, and marijuana. Current abstinence at follow-up from marijuana was 61% and 81%, respectively. The use of aversion therapy for both alcohol and cocaine in alcoholics who were also using cocaine was associated with higher total abstinence rates (88% vs. 55%) from cocaine when compared with alcoholics who used cocaine but received no aversion as part of their program. The conclusion is tentative since the follow-up rate in this study was lower than that of the previous study (64% vs. 84%). Being around other users accounted for 49% of relapse situations. Family/Work stress was associated with relapse in 33% of cases and unpleasant feelings in 24% of cases. The use of both reinforcement treatments and the use of support following treatment were associated with improved abstinence rates from cocaine. Those patients who reported losing all urges for cocaine after treatment had a total abstinence from cocaine of 90%, those who reported losing all the uncontrollable urges had a total abstinence of 64%, and those who reported still having the urge reported only 33% total abstinence from cocaine.