Current Psychopharmacology - Volume 9, Issue 1, 2020

Background: The search for an accurate, gene-based test to identify heritable risk factors for Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published studies about the role of dopamine in addictive behaviors, including risk for drug dependence and compulsive/impulsive behavior disorders. The term RDS was first coined by Blum’s group in 1995 to identify a group of behaviors with a common neurobiological mechanism associated with a polymorphic allelic propensity for hypodopaminergia. Objectives: To outline the process used to select risk alleles of reward genes for the Genetic Addiction Risk Score (GARS) test. Consequently, to address the limitations caused by inconsistent results that occur in many case-control behavioral association studies. These limitations are perhaps due to the failure of investigators to adequately screen controls for drug and alcohol use disorder, and any of the many RDS behaviors, including nicotine dependence, obesity, pathological gambling, and internet gaming addiction. Methods: Review of the literature related to the function of risk alleles of reward genes associated with hypodopaminergia relevant case-control association studies for the selection of alleles to be measured by the Genetic Addiction Risk Score (GARS) test. Results: The prevalence of the DRD2 A1 allele in unscreened controls (33.3%), compared to “Super-Controls” [highly screened RDS controls (3.3%) in proband and family] is used to exemplify a possible solution. Conclusion: Unlike One Gene-One Disease (OGOD), RDS is polygenetic, and very complex. In addition, any RDS-related behaviors must be eliminated from the control group in order to obtain the best possible statistical analysis instead of comparing the phenotype with diseaseridden controls.

Background: Alzheimer’s disease is the most common neurodegenerative disorder affecting the elderly population and emerges as a leading challenge for the scientific research community. The wide pathological aspects of AD made it a multifactorial disorder and even after long time it’s difficult to treat due to unexplored etiological factors. Methods: The etiogenesis of AD includes mitochondrial failure, gut dysbiosis, biochemical alterations but deposition of amyloid-beta plaques and neurofibrillary tangles are implicated as major hallmarks of neurodegeneration in AD. The aggregates of these proteins disrupt neuronal signaling, enhance oxidative stress and reduce activity of various cellular enzymes which lead to neurodegeneration in the cerebral cortex, neocortex and hippocampus. The metals like copper, aluminum are involved in APP trafficking and promote amyloidbeta aggregation. Similarly, disturbed ubiquitin proteasomal system, autophagy and amyloid- beta clearance mechanisms exert toxic insult in the brain. Results and Conclusion: The current review explored the role of oxidative stress in disruption of amyloid homeostasis which further leads to amyloid-beta plaque formation and subsequent neurodegeneration in AD. Presently, management of AD relies on the use of acetylcholinesterase inhibitors, antioxidants and metal chelators but they are not specific measures. Therefore, in this review, we have widely cited the various pathological mechanisms of AD as well as possible therapeutic targets.

Background: Holarrhena antidysenterica is a deciduous shrub/small-tree having bioactive alkaloids such as conessine, known for astringent, antidysenteric, anthelmintic, stomachic, febrifugal, tonic and anti-acetylcholinesterase properties. Dementia is an age related neurodegenerative syndrome with Alzheimer’s disease, the most prominent cause, which has limited therapeutic options available. Objective: The present study aimed to explore the potential benefits of H. antidysenterica in the management of dementia. Methods: Aqueous and methanol extracts of powdered bark of H. antidysenterica were prepared, concentrated and conessine concentration was estimated using High Performance Thin Layer Chromatography (HPTLC) method. Methanol extract of H. antidysenterica (MEHA) was administered at doses 100, 150 and 200 mg/kg (i.p.) to mice (20-30 g) for 14 consecutive days. Scopolamine (Scop; 1 mg/kg) and Lipopolysaccharide (LPS; 250 μg/kg) were given (i.p.) before behavioural trials to induce memory impairment. Learning and memory functions in mice were evaluated. Brain acetylcholinesterase (AChE) activity, glutathione (GSH) and Thiobarbituric Acid Reactive substances (TBARS) levels were estimated. Results: MEHA markedly increased learning and memory of mice. Scop or LPS caused a significant decline of spatial memory in mice, which was attenuated by MEHA (100 and 200 mg/kg). Furthermore, LPS conspicuously increased the lipid peroxidation and compromised antioxidant levels in mice brains. MEHA pre-treatment significantly increased GSH content and decreased TBARS level in the brain of LPS administered mice. AChE activity was significantly decreased by MEHA in the brain of mice. Conclusion: The methanol extract of H. antidysenterica may prove to be a useful remedy in the management of dementia.

Background: Depression disorder has been considered to be the global common psychological CNS disorder affecting about 121 million people worldwide and is among the leading causes of disability that not only inflicts suffering but also carries a high economic burden. Calendula officinalis L. (Marigold) is globally known for its medicinal importance containing various phytochemicals including terpenoids, quinones, coumarins and other constituents, showing some important biological activities like immuno-stimulant, hepatoprotective, antioxidant, etc. activities with no toxic effect. Objective: This study aims to evaluate the antidepressant effect of ethanolic extract of Calendula officinalis using rodent models (Wistar rat) of depression. Methods: The present study was carried out to evaluate the antidepressant effect of ethanolic extract of Calendula officinalis in Wistar rat. This effect was determined by recording the immobility time in Forced Swim Test (FST) and a number of squares crossing and rearing in Open Field Test (OFT). The rats were randomly divided into 5 groups. Rats belonged to group 1 act as control group and group 2 were given Imipramine (10 mg/kg, i.p.) which act as standard group.Wistar rats were treated i.p. with Ethanolic extract of Calendula officinalis group 3, 4 and 5 were given 100mg/kg, 200mg/kg and 400mg/kg respectively. Results: The effect of rat model of depression i.e. Forced Swim Test (FST) and Open Field Test (OFT) model indicated that Ethanolic extract of Calendula officinalis showed potent to moderate antidepressant effect (decrease in immobility time and increase in number of square crossing and rearing) as compared to normal group. The drug might act as monoamine oxidase inhibitors. Conclusion: Taken all together, the present study concluded that the drug EECO was to exert antidepressant effects by inhibiting the monoamine oxidase-A (MAO-A) reaction, which is responsible for the regulation of the metabolism of the neurotransmitter 5-hydroxytryptamine (5-HT) in the brain. This drug might act as monoamine oxidase inhibitors (MAO-inhibitors) hence may increase the levels of norepinephrine, dopamine and serotonin; and decrease the levels of GABA in the brain.

Background: Previous research from our laboratory implicated opioid and benzodiazepine- GABA mechanisms in other effects of N2O (antinociception and anxiolysis), so a decision was made to study these as potential mechanisms of N2O-induced dysfunction of spatial working memory. Objective: to explore potential mechanisms of N2O in reducing spatial working memory in mice. Methods: we monitored spontaneous alternation behavior (SAB) in male NIH Swiss mice exposed to N2O during a T-maze spontaneous alternation task (T-SAT). Results: mice that were exposed to 70% N2O (in O2) exhibited severely and significantly reduced spontaneous alternation behavior in the T-SAT. Mice in this environment alternated their route only 33% of the time, in comparison to the control (room air) rate of alternation at approximately 70%. Mice pretreated with the benzodiazepine antagonist, flumazenil exhibited a dose-dependent restoration of spatial working memory under 70% N2O in the T-SAT. Alternatively, pretreatment with neither the GABAA antagonist gabazine nor the opioid antagonist naloxone had any appreciable effect on the N2O-reduced SAB. Conclusion: this study verified that 70% N2O can reduce spatial working memory in mice, which appears to involve benzodiazepine mechanisms in the brain.