Activation of CB1 Receptors May Provide an Effective Treatment for Obsessive Compulsive Disorder
Obsessive compulsive disorder (OCD) is an anxiety disorder characterized by mental obsessions and compulsions stemming from chemical imbalances in the brain. Drugs that facilitate serotonin transmission are commonly used to treat OCD, but they can become ineffective with prolonged use. It has been suggested that CB1 (cannabinoid type 1) receptors are an alternative drug target that could provide effective treatment. The aims of this study were to investigate more successful longer-term drug treatment options for anxiety-based symptoms of OCD and to better understand serotonin’s interaction with CB1. This study used an 11-day marble burying behavioral model with three groups of mice treated respectively with saline, WIN 55,212-2 (CB1 agonist), or Tianeptine (5-HT antagonist; Tianeptine and WIN 55,212-2 days 6-10). Mice receiving the CB1 agonist buried fewer marbles than did the control with no deterioration of effect over ten days. Mice receiving both Tianeptine and WIN 55,212-2 also buried fewer marbles. These results indicate that WIN 55,212-2 has anxiolytic properties that could be an effective treatment for the compulsive symptoms of OCD. It also suggests that CB1 receptors are situated downstream of serotonin receptors.
https://www.ncbi.nlm...pubmed/23036485Animal models of chronic stress represent valuable tools by which to investigate the behavioral, endocrine and neurobiological changes underlying stress-related psychopathologies, such as major depression, and the efficacy of antidepressant therapies. The present study was aimed at investigating the neurochemical effects of the antidepressant tianeptine in rats exposed to the chronic stress model. To this aim, rats were subjected to 40days of chronic unpredictable stressful stimuli, after which the animals received saline or tianeptine (15mg/kg) once a day for 7days. Additionally, IL-6, IL-1, TNF-α levels and oxidative stress parameters were assessed in the prefrontal cortex (PFC), hippocampus (HPC), amygdala (AMY) and nucleus accumbens (NAc) in all of the experimental groups studied. The results indicated that chronic mild stress and tianeptine did not exercise any effects on cytokines in all of the structures studied; in the PFC and AMY thiobarbituric acid reactive substances (TBARS) levels were decreased in control rats treated with tianeptine in the HPC; superoxide dismutase (SOD) activity was found to have decreased in stressed rats treated with saline in the PFC, HPC, AMY and NAc, and tianeptine reversed this effect; catalase (CAT) activity was found to have decreased in the PFC, HPC and NAc of stressed rats treated with saline, but was shown to have increased in stressed rats treated with tianeptine, and tianeptine also reversed the decreases in CAT activity in stressed rats treated with saline, suggesting that tianeptine exerted antioxidant activity. In conclusion, the present findings open new vistas on the pharmacological activity of tianeptine, in particular, concerning its ability to attenuate oxidative stress.
https://www.longecit...adhddepression/https://www.ncbi.nlm...les/PMC4662168/ The dopaminergic system is correlated with increased gray matter volume in the dorsolateral prefrontal cortex and striatal regions, which are associated with creativity.1) The antidepressant bupropion inhibits dopamine and norepinephrine reuptake. Buproprion led to significant improvement in our patient’s depression symptoms and significant increases in gray matter, white matter, and total brain volumes. The dopamine and norepinephrine agonist methamphetamine can also increase gray matter volume in the right putamen, which is associated with better inhibitory control.2) Apart from these dopamine-related mechanisms, bupropion probably also changes gray matter volume by preventing oxidative stress related to major depressive disorder,3) or by modulating glutamate receptor function.4) Gray matter volume might increase for several reasons: synaptic remodeling and neurogenesis;5) stimulation of neurotrophic factors by antipsychotics;6) prevention of oxidative stress or 6-OH-dopamine lesioning with subsequent increased glial cell proliferation in the frontal cortex;7) or modulation of glutamate receptor function.8)
One concern with these results is the variability of the SIENA method. A longitudinal survey comparing different segmentation methods found that SIENA gives large, heterogeneous values for brain volume changes, implying the variability of this method.9) Another study mentioned that SIENA could use the outer skull surface for both time points to reduce the effects of scanner drift and inter-scanner variability on longitudinal morphometric results.10) Therefore, our method still had some value for assessing longitudinal changes with bupropion treatment. This evidence of increased gray matter and total brain volumes with bupropion treatment has clinical implications for the possible effects of norepinephrine and dopamine reuptake inhibition on brain structure in the treatment of depression.
In conclusion, the treatment of depression with bupropion appears to be accompanied by changes in the gray matter, white matter, and total brain volumes.
https://www.reddit.c...ach_antagonism/https://www.ncbi.nlm...pubmed/1319912/The effects of L-alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced memory impairment and on brain acetylcholine (ACh) synthesis and release were investigated in rats. Oral administration of alpha-GPC 3 h before the behavioural test prevented the learning impairment induced by scopolamine given 30 min before the acquisition of a passive avoidance response. Similarly, retrograde amnesia induced by scopolamine, given immediately after acquisition training, was also completely reversed by the drug. These effects were dose-dependent with a maximum at 300 mg/kg. The mechanism of action of this compound was investigated by measuring hippocampal ACh synthesis and release both in vivo by means of the microdialysis technique and in vitro in tissue slices. alpha-GPC dose dependently increased ACh release with a maximum at 300 mg/kg. In addition, i.v. injection of [14C]alpha-GPC resulted in [14C]ACh formation. The data suggest that the behavioural effects of alpha-GPC may be related to its property to increase hippocampal ACh synthesis and release.
PMID: 1319912
https://www.ncbi.nlm...les/PMC3669033/Background
Eurycoma longifolia is a medicinal plant commonly called tongkat ali (TA) and “Malaysian ginseng.” TA roots are a traditional “anti-aging” remedy and modern supplements are intended to improve libido, energy, sports performance and weight loss. Previous studies have shown properly-standardized TA to stimulate release of free testosterone, improve sex drive, reduce fatigue, and improve well-being.
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Methods
We assessed stress hormones and mood state in 63 subjects (32 men and 31 women) screened for moderate stress and supplemented with a standardized hot-water extract of TA root (TA) or Placebo (PL) for 4 weeks. Analysis of variance (ANOVA) with significance set at p < 0.05 was used to determine differences between groups.
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Results
Significant improvements were found in the TA group for Tension (−11%), Anger (−12%), and Confusion (−15%). Stress hormone profile (salivary cortisol and testosterone) was significantly improved by TA supplementation, with reduced cortisol exposure (−16%) and increased testosterone status (+37%).
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Conclusion
These results indicate that daily supplementation with tongkat ali root extract improves stress hormone profile and certain mood state parameters, suggesting that this “ancient” remedy may be an effective approach to shielding the body from the detrimental effects of “modern” chronic stress, which may include general day-to-day stress, as well as the stress of dieting, sleep deprivation, and exercise training.
https://www.hindawi....i/2017/7949582/ Central nervous system (CNS) senses energy homeostasis by integrating both peripheral and autonomic signals and responding to them by neurotransmitters and neuropeptides release. Although it is previously considered an immunologically privileged organ, we now know that this is not so. Cells belonging to the immune system, such as B and T lymphocytes, can be recruited into the CNS to face damage or infection, in addition to possessing resident immunological cells, called microglia. In this way, positive energy balance during obesity promotes an inflammatory state in the CNS. Saturated fatty acids from the diet have been pointed out as powerful candidates to trigger immune response in peripheral system and in the CNS. However, how central immunity communicates to peripheral immune response remains to be clarified. Recently there has been a great interest in the neuropeptides, POMC derived peptides, ghrelin, and leptin, due to their capacity to suppress or induce inflammatory responses in the brain, respectively. These may be potential candidates to treat different pathologies associated with autoimmunity and inflammation. In this review, we will discuss the role of lipotoxicity associated with positive energy balance during obesity in proinflammatory response in microglia, B and T lymphocytes, and its modulation by neuropeptides
https://www.ncbi.nlm...pubmed/17762517 It has been shown that music might be able to improve mood state in people affected by psychiatric disorders, ameliorate cognitive deficits in people with dementia and increase motor coordination in Parkinson patients. Robust experimental evidence explaining the central effects of music, however, is missing. This study was designed to investigate the effect of music on brain neurotrophin production and behavior in the mouse. We exposed young adult mice to music with a slow rhythm (6 h/day; mild sound pressure levels, between 50 and 60 db) for 21 consecutive days. At the end of the treatment, mice were tested for passive avoidance learning and then killed for analysis of brain-derived neurotrophic factor (BDNF) and nerve growth factor with enzyme-linked immunosorbent assay (ELISA) in selected brain regions. We found that music-exposed mice showed increased BDNF, but not nerve growth factor in the hippocampus. Furthermore, we observed that music exposure significantly enhanced learning performance, as measured by the passive avoidance test. Our results demonstrate that exposure to music can modulate the activity of the hippocampus by influencing BDNF production. Our findings also suggest that music exposure might be of help in several central nervous system pathologies.
https://www.scienced...361923016300090 Previous research has shown that dorsal hippocampus plays an important role in spatial memory process. Music exposure can enhance brain-derived neurotrophic factor (BDNF) expression level in dorsal hippocampus (DH) and thus enhance spatial cognition ability. But whether music experience may affect different subregions of DH in the same degree remains unclear. Here, we studied the effects of exposure to Mozart K.448 on learning behavior in developing rats using the classical Morris water maze task. The results showed that early music exposure could enhance significantly learning performance of the rats in the water maze test. Meanwhile, the BDNF/TrkB level of dorsal hippocampus CA3 (dCA3) and dentate gyrus (dDG) was significantly enhanced in rats exposed to Mozart music as compared to those without music exposure. In contrast, the BDNF/TrkB level of dorsal hippocampus CA1 (dCA1) was not affected. The results suggest that the spatial memory improvement by music exposure in rats may be associated with the enhanced BDNF/TrkB level of dCA3 and dDG.
https://www.scienced...55041311630554XUnder an Elsevier user license
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The global epidemic of obesity and its associated chronic diseases is largely attributed to an imbalance between caloric intake and energy expenditure. While physical exercise remains the best solution, the development of muscle-targeted “exercise mimetics” may soon provide a pharmaceutical alternative to battle an increasingly sedentary lifestyle. At the same time, these advances are fueling a raging debate on their escalating use as performance-enhancing drugs in high-profile competitions such as the Olympics.
https://www.fightagi...-mimetic-drugs/ The field of exercise mimetics is still young, but quite similar at the high level to the more established attempts to find drugs that mimic portions of the calorie restriction response. Exercise and calorie restriction are the two most obvious, well-studied, and reliable means of adjusting the operation of metabolism in order to improve health and extend healthy life span. Sadly, the long-term effects on life span in long-lived species such as our own are nowhere near as large as those exhibited by short-lived species such as laboratory mice. Nonetheless, given that exercise and calorie restriction produce benefits that are larger and more robust than anything that can be achieved for healthy people with presently available medical technology (a state of affairs that we hope will soon change), there is considerable interest in developing drugs that can achieve similar outcomes. In principle at least, these altered states of metabolism have points of control and regulation, a small number of proteins and genes that can be targeted by therapeutics.
https://www.the-scie...romotes-Memory/ Working out is good for the brain. Now, a team of scientists from the U.S. and Germany has a clearer idea why. A protein called cathepsin B, produced and secreted by muscle during exercise, is required for exercise-induced memory improvement and brain cell production in mice, the scientists reported in Cell Metabolism today (June 23). They also showed that levels of cathepsin B are positively correlated with fitness and memory in humans.