Garcinia camobogia extract alters anxiety, sociability, and dopamine turnover in male Swiss albino mice

Obesity is a global concern, closely allied with somatic and psychosomatic disorders. Herbal drugs are available in modern medicine to treat obesity. Garcinia camobogia being used by so many people trying to lose weight produces various systemic side effects. The study was conducted to assess its effect on anxiety, sociability, and dopamine turnover in male mice. Twenty-one male Swiss albino mice of either were divided into three groups with seven mice in each group. Control group was given distilled water (0.5 ml p.o.) and the other two groups received Garcinia cambogia extract at two different doses, a low and a higher dose (100 mg/kg and 500 mg/kg. p.o.) Each animal received a single oral dose daily, which was administered using an oral gavage for fourteen consecutive days. Effect of test drugs on anxiety was evaluated using open field test. Sociability and social novelty were evaluated using three chambers test. Results (mean ± SD) were analyzed using one-way ANOVA test followed by Tukey’s test. Garcinia cambogia extract significantly increased the time spent in the corners in the open field test, significantly reduced sociability and social novelty in the three-chamber test, significantly reduced dopamine turnover in the brain with a significant decrease in dopamine metabolite homovanillic acid (HVA) and increased D2 receptor expression in ventral tegmental area. Garcinia cambogia extract have significant anxiogenic effect along with reduced sociability and social novelty in male mice. Moreover, these effects could be related to the altered dopamine turnover and D2 receptor expression in mice brain. Article Highlights Chronic used of alcoholic extract of Garcinia campbogia lead to a significant increase in anxiety that was manifested by the reduced time in the center zone and increased immobility in the open field test. Garcinia camobogia chronic administration has a profound impact on sociability and social novelty with a significant decrease in both behavioral patterns compared to the control group. These effects could be attributed to the noticed change in the dopamine turnover in the brain with a significant decrease in dopamine metabolite (HVA) and an upward expression of D2 receptors in return.

Garcinia Camobogia Extract Alters Anxiety, Sociability, and Dopamine Turnover in Male Swiss Albino Mice

Background: Obesity is a global concern, closely allied with somatic and psychosomatic disorders. Herbal drugs are available in modern medicine to treat obesity. Garcinia camobogia being used by so many people trying to lose weight produces various systemic side effects. The study was conducted to assess its effect on anxiety, sociability, and dopamine turnover in male mice. Methodology: Male Swiss albino mice of either were divided into three groups with seven mice in each group. Different groups were given distilled water (0.5ml p.o.) and Garcinia cambogia extract at two different doses (100mg/kg and 500 mg/kg p.o.). Effect of test drugs on anxiety was evaluated using open field test. Sociability and social novelty were evaluated using three chambers test. Results (mean ± standard deviation) were analyzed using one-way ANOVA test followed by Tukey’s test. Result: Garcinia cambogia extract significantly increased the time spent in the corners in the open field test, significantly reduced sociability and social novelty in the three chamber test, significantly reduced dopamine turnover and increased D2 receptor expression in ventral tegmental area. Conclusion: Garcinia cambogia extract have significant anxiogenic effect along with reduced sociability and social novelty in male mice. Moreover, these effects could be related to the altered dopamine turnover and D2 receptor expression in mice brain.

DOPAMINERGIC SYSTEM OF THE HYPOTHALAMUS AND STRIATUM OF THE RAT BRAIN WITH THE COMBINED EFFECTS OF ACUTE ALCOHOL INTOXICATION AND PHYSICAL INACTIVITY

Background. The growth of industrialization is accompanied by a decrease in human motor activity, and chronic stress increases the risk of alcoholism. The combination of these factors has a negative effect on the physiological and biochemical processes in the body. Purpose of work. To determine the state of the components of the dopaminergic system in the hypothalamus and striatum of rats during acute alcoholization against the background of hypodynamia. Material and methods. The experiment was carried out on male rats weighing 180-200 g, which, after hypodynamia for a period of 7, 14 and 28 days, were once injected with 25% alcohol at a dose of 3.5 g / kg. The content of the components of the dopaminergic system was determined by high performance liquid chromatography. Results. The striatum is characterized by a decrease in the activity of the dopaminergic system on the 7th day of hypodynamia, followed by its activation with an increase in the period of immobilization to 28 days. In the hypothalamus in the early stages of hypodynamia with subsequent OAI, the changes are poorly expressed, however, on the 28th day, dopamine turnover is activated. Conclusions. The combined effect of acute alcohol intoxication and hypodynamia leads to more pronounced changes in the dopaminergic system in the striatum than in the hypothalamus. Acute alcohol intoxication has a stimulating effect on the dopaminergic system of the hypothalamus and striatum only for long periods of hypodynamia (28 days).

On the learning of addictive behavior: Sensation-seeking propensity predicts dopamine turnover in dorsal striatum

We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis. We previously determined dopaminergic receptor density in striatum, and we now tested the hypothesis that an elevated dopaminergic condition with increased extracellular dopamine and receptor density follows increased dopamine synthesis capacity in highly sensation-seeking individuals, as measured by positron emission tomography of 18 men with tracer fluorodopa (FDOPA). We detected a site in left caudate nucleus where the volume of distribution of FDOPA-derived metabolites correlated negatively with FDOPA metabolite turnover, consistent with decreased metabolite breakdown in highly sensation-seeking subjects. High rates of sensation-seeking attenuated the dopamine turnover in association with a low rate of dopamine recycling, low dopamine oxidation, and elevated extracellular dopamine and receptors in caudate nucleus. In contrast, low rates of sensation-seeking were associated with rapid dopamine recycling, rapid dopamine oxidation, low extracellular dopamine, and low receptor density. We conclude that the modulation of dopaminergic neurotransmission associated with sensation-seeking is a state of sensation-seeking, rather than a trait of personality following abnormal regulation of dopaminergic neurotransmission.

Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf

Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.

THE STATE OF THE DOPAMINERGIC SYSTEM OF THE RATS’ BRAIN IN THE MORPHINE-ALCOHOLIC POST-INTOXICATION SYNDROME

Background. Opioid addiction, which has arisen against the background of previous alcoholism (or vice versa), is an urgent problem in clinical practice. The change in dopaminergic neuromediation after the withdrawal of the combined effect of ethanol and morphine is currently not clear what was the goal for our study. Purpose. Study of metabolites of the dopaminergic system in the cerebral cortex, striatum and midbrain of rats after different periods of withdrawal of 5-day morphine-alcohol intoxication. Material and methods. The experiments were carried out on 43 white outbred male rats. Using the HPLC method, the levels of metabolites of the dopaminergic system were determined after the withdrawal of the combined administration of morphine and ethanol. Results and conclusions. The severity of changes in metabolites of the dopaminergic system during morphinealcohol withdrawal is determined by the duration and region of the brain. One day after the withdrawal of both psychoactive substances in the striatum and cerebral cortex, a decrease in the concentration of dopamine was observed. In the long-term periods of abolition of intoxication with morphine and ethanol (3, 7 days), the processes of acceleration of dopamine turnover in the midbrain and a decrease in the concentration of the neurotransmitter in the striatum were revealed.

Embryonic Thermal Manipulation Affects Ventilation, Metabolism, Thermal Control and Central Dopamine in Newly Hatched and Juvenile Chicks

The first third of incubation is critical for embryonic development, and environmental changes during this phase can affect the physiology and survival of the embryos. We evaluated the effects of low (LT), control (CT), and high (HT) temperatures during the first 5 days of incubation on ventilation (V.E), body temperature (Tb), oxygen consumption (V.O2), respiratory equivalent (V.E/V.O2), and brain monoamines on 3-days-old (3d) and 14-days-old (14d) male and female chickens. The body mass of LT animals of both ages and sexes was higher compared to HT and CT animals (except for 3d males). The heart mass of 14d HT animals was higher than that of CT animals. Thermal manipulation did not affect V.E, V.O2 or V.E/V.O2 of 3d animals in normoxia, except for 3d LT males V.E, which was lower than CT. Regarding 14d animals, the HT females showed a decrease in V.E and V.O2 compared to CT and LT groups, while the HT males displayed a lower V.O2 compared to CT males, but no changes in V.E/V.O2. Both sexes of 14d HT chickens presented a greater Tb compared to CT animals. Thermal manipulations increased the dopamine turnover in the brainstem of 3d females. No differences were observed in ventilatory and metabolic parameters in the 3d animals of either sexes, and 14d males under 7% CO2. The hypercapnic hyperventilation was attenuated in the 14d HT females due to changes in V.O2, without alterations in V.E. The 14d LT males showed a lower V.E, during hypercapnia, compared to CT, without changes in V.O2, resulting in an attenuation in V.E/V.O2. During hypoxia, 3d LT females showed an attenuated hyperventilation, modulated by a higher V.O2. In 14d LT and HT females, the increase in V.E was greater and the hypometabolic response was attenuated, compared to CT females, which resulted in no change in the V.E/V.O2. In conclusion, thermal manipulations affect hypercapnia-induced hyperventilation more so than hypoxic challenge, and at both ages, females are more affected by thermal manipulation than males.

Changes in the dopaminergic system in the hypothalamus and midbrain of rats at chronic complex alcohol-morphine intoxication

Recently, there have been more and more indications of alcoholic pathology burdened by drug use and vice versa. It is evident that the dopamine system plays an important role in the development of addiction when using drugs and alcohol. Experimentally, the long-term combined effect of psychoactive substances on neuromendatory changes in the dopaminergic system in the brain is poorly understood and requires more detailed consideration.The aim of the study was to examine the changes in the dopaminergic system in the hypothalamus and midbrain of rats during chronic alcohol intoxication, as well as a complex administration of morphine and ethanol.The experiments were carried out on white outbred male rats. Using the HPLC method, the levels of dopamine and its metabolites were determined in the regions of the brain during chronic alcohol intoxication, as well as with a combined administration of morphine and ethanol with various durations (7, 14 and 21 days).Chronic alcohol intoxication led to the signs of acceleration of the dopamine turnover only in the hypothalamus on the 7th and 14th days and its accumulation during three weeks of alcoholization. In the midbrain, a decrease in the concentration of the neurotransmitter was revealed when ethanol was injected for 7 days. Co-administration of surfactants was accompanied by slightly different changes: complex 7- and 21-day alcohol-morphine intoxication is accompanied by the dopamine accumulation in the hypothalamus and the decrease in the neurotransmitter turnover in the midbrain on the 14th and 21st days.

Dynamic control of the dopamine transporter in neurotransmission and homeostasis

The dopamine transporter (DAT) transports extracellular dopamine into the intracellular space contributing to the regulation of dopamine neurotransmission. A reduction of DAT density is implicated in Parkinson’s disease (PD) by neuroimaging; dopamine turnover is dopamine turnover is elevated in early symptomatic PD and in presymptomatic individuals with monogenic mutations causal for parkinsonism. As an integral plasma membrane protein, DAT surface expression is dynamically regulated through endocytic trafficking, enabling flexible control of dopamine signaling in time and space, which in turn critically modulates movement, motivation and learning behavior. Yet the cellular machinery and functional implications of DAT trafficking remain enigmatic. In this review we summarize mechanisms governing DAT trafficking under normal physiological conditions and discuss how PD-linked mutations may disturb DAT homeostasis. We highlight the complexity of DAT trafficking and reveal DAT dysregulation as a common theme in genetic models of parkinsonism.