Korean Red Ginseng inhibits methamphetamine addictive behaviors by regulating dopaminergic and NMDAergic system in rodents.

BACKGROUND: Methamphetamine (METH) is the most widely used psychostimulant and has been known to exhibit reinforcing effects even after long abstinence. We showed the inhibitory effect of Korean Red Ginseng extract (RGE) on METH-induced addictive behaviors in animal models mimicking the human drug-use pattern. METHODS: We first investigated the effect of RGE on the acquisition of METH-induced dependence using self-administration and conditioned place preference (CPP) tests. Additionally, further experiments such as METH-induced motivational behavior and seeking behavior were conducted. To study the underlying mechanism, dopamine receptor, dopamine transporter, and N-methyl-D-aspartate receptor were assessed through Western blot analysis. RESULTS: Treatment with RGE significantly reduced METH-induced self-administration on a fixed-ratio 1 schedule of reinforcement. It could be also decreased a progressive ratio schedule, and inhibited METH-primed reinstatement. In CPP, RGE significantly prevented the development of METH-induced CPP. Moreover, RGE not only shortened the withdrawal period clearly, but also prevented the reinstatement of CPP. RGE treatment also reversed METH-induced overexpression of dopamine transporter, dopamine receptor D1, and NMDA receptor in the nucleus accumbens. CONCLUSION: Our findings reflect that RGE has therapeutic potential to suppress METH-induced addictive behaviors by regulating dopaminergic and NMDAergic system.

Methoxphenidine (MXP) induced abnormalities: Addictive and schizophrenia-related behaviours based on an imbalance of neurochemicals in the brain.

BACKGROUND AND PURPOSE: Methoxphenidine is a dissociative-based novel psychoactive designer drug. Although fatal accidents from methoxphenidine abuse have been reported, recreational use of the drug continues. We aim to provide scientific supportfor legal regulation of recreational abuse of methoxphenidine by demonstrating its the pharmacological action. EXPERIMENTAL APPROACH: Addictive potential of methoxphenidine was examined using intravenous self-administration test with rats and conditioned place preference test with mice. Further, a series of behavioural tests (open field test, elevated plus maze test, novel object recognition test, social interaction test and tail suspension test) performed to assess whether methoxphenidine caused schizophrenia-related symptoms in mice. Additionally, neurotransmitter enzyme-linked immunosorbent assay and western blot were used to confirm methoxphenidine-induced neurochemical changes in specific brain regions related to abnormal behaviours. KEY RESULTS: Methoxphenidine caused addictive behaviours via reinforcing and rewarding effects. Consistently, methoxphenidine induced over-activation of dopamine pathways in the nuclear accumbens, indicating activation of the brain reward circuit. Also, methoxphenidine caused all categories of schizophrenia-related symptoms, including positive symptoms (hyperactivity, impulsivity), negative symptoms (anxiety, social withdrawal, depression) and cognitive impairment. Consistently, methoxphenidine led to the disruption of the hippocampal-prefrontal cortex pathway that is considered to be pathological involved in schizophrenia. CONCLUSIONS AND IMPLICATIONS: We demonastrate that methoxphenidine causes addictive and schizophrenia-like behaviours and induces neurochemical changes in brain regions associated with these behaviours. We propose that methoxphenidine could be used in developing useful animal disease models and that it also requires legal restrictions on its recreational use.

New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents.

2C (2C-x) is the general name for the family of phenethylamines containing two methoxy groups at the 2 and 5 positions of the benzene ring. The abuse of 2C family drugs has grown rapidly, although the abuse potential and neurotoxic properties of 2C drugs have not yet been fully investigated. In this study, we investigated the abuse potential and neurotoxicity of 4-chloro-2,5-dimethoxyphenethylamine (2C-C) and 2,5-dimethoxy-4-propylphenethylamine (2C-P). We found that 2C-C and 2C-P produced conditioned place preference in a dose-dependent manner in mice, and increased self-administration in rats, suggesting that 2C-C and 2C-P have abuse potential. To investigate the neurotoxicity of 2C-C and 2C-P, we examined motor performance and memory impairment after high doses of 2C-C and 2C-P. High doses of 2C-C and 2C-P decreased locomotor activity, rota-rod performance, and lower Y-maze test, novel objective recognition test, and passive avoidance test scores. We also observed that 2C-C and 2C-P affected expression levels of the D1 dopamine receptor, D2 dopamine receptor, dopamine transporter, and phospho-dopamine transporter in the nucleus accumbens and the medial prefrontal cortex, and increased c-Fos immuno-positive cells in the nucleus accumbens. Moreover, high doses of 2C-C and 2C-P induced microglial activation, which is involved in the inflammatory reaction in the striatum. These results suggest that 2C-C and 2C-P have abuse potential by affecting dopaminergic signaling and induce neurotoxicity via initiating neuroinflammation at high doses.

Prevalence of intimate partner violence victimization and its association with mental disorders in the Korean general population.

This study assessed the association between experiencing physical or sexual intimate partner violence (IPV) and mental health among women in the general Korean population. A total of 3160 South Korean women aged 18 to 74 responded to the Korean version of the WHO-Composite International Diagnostic Interview (K-CIDI), version 2.1., and questions about IPV. Multiple logistic regression was used to examine the odds of developing mental disorders associated with each type of IPV. Victimization by any type of IPV was associated with significantly increased odds of experiencing any mental disorders in the lifetime (OR 4.4, 95% CI 2.4-8.0). Participants who experienced sexual IPV had the highest odds of having mental disorders (OR 14.3, 95% CI 4.1-54.8). Sexual IPV experience among participants was associated with higher odds of major depressive disorder, anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, specific phobias, agoraphobia, and nicotine dependence. Alcohol use disorder was highly associated with experiencing physical IPV (OR 3.8, 95% CI 1.7-8.0). Among women who experienced IPV, the youngest age group, from 18 to 35 years old (2.6%, 95% CI 1.4-3.8), and the never married group (2.7%, 95% CI 1.2-4.2) experienced the highest proportion of any form of IPV. Mental disorders throughout the lifetime are highly associated with the experience of IPV among women and are most prevalent among those who experienced sexual IPV. Thus, to prevent mental disorders among female IPV victims, treatment specific to each type of IPV should be provided early.

Age-related differences in the influence of major mental disorders on suicidality: a Korean nationwide community sample.

BACKGROUND: We compared the influence of major mental disorders on suicidality according to age, adjusting for suicide-related correlates. METHODS: This study was based on the Korean national epidemiological survey of mental disorders including community-dwelling adults between 18 and 74 years of age (n=6022). Subjects were classified into three age groups; young (18-39), middle-aged (40-59), and late adulthood (60-74). Face-to-face interviews were conducted using the Korean version of the Composite International Diagnostic Interview. According to age groups, the influence of major depressive disorder (MDD), anxiety disorder, and alcohol use disorder on risk for suicidality were investigated by multiple logistic regression models adjusting for sex, years of education, marital status, income, employment, presence of chronic medical illness, and lifetime history of suicide attempt. RESULTS: After including MDD as a covariate, anxiety disorder remained a risk factor only in the middle-aged group (adjusted OR: 2.83, 95% CI: 1.54-5.22), and alcohol use disorder was a risk factor for suicidality only in the young group (adjusted OR: 2.81, 95% CI: 1.06-7.43). Conversely, MDD was the only mental disorder that significantly increased suicidality in all age groups. LIMITATIONS: This was a cross-sectional study and did not include subjects over 75 years of age. CONCLUSION: This study showed that the contribution of psychiatric disorders to risk for suicidality varied according to age group. Therefore, strategies for suicide prevention should be specifically designed for different age groups.