Neurotransmitters and neuromodulators involved in learning and memory

Learning and memory being highly specialized process of human brain involves complex interaction between neurotransmitters and cellular events. Over the years, the understandings of these processes have been evolving from psychological, neurophysiological, and pharmacological perspectives. The most widely appraised model of learning and memory involves attention, acquisition, storage and retrieval. Each of these events involve interplay of neurotransmitters such as dopamine, acetylcholine, norepinephrine, N-methyl-d-aspartic acid, gamma-aminobutyric acid, though preponderance of specific neurotransmitter have been documented. The formation of long-term memory involves cellular events with neuroplasticity. Further, dopamine is documented to play crucial role in the process of forgetting. Understanding of the processes of learning and memory not only facilitates drug discovery, but also helps to understand actions of several existing drugs. In addition, it would also help to enhance psychological interventions in children with learning disabilities. Thus, the review intends to summarize role of neurotransmitters and neuromodulators during different phases of learning and memory

INFLUENCE OF ZINCOVIT DROP (NUTRITIONAL FOOD SUPPLEMENT) ON IMMUNE SYSTEM IN NORMAL AND CYCLOPHOSPHAMIDE INTOXICATED WISTAR RATS

ABSTRACTObjective: The aim of the present study was to investigate the influence of Zincovit (ZVT) drop (nutritional food supplement) on the immune systemin normal healthy and cyclophosphamide (CP) intoxicated Wistar rats.Methods: The study was carried out in healthy and immunotoxic Wistar rats (CP; 20 mg/kg/day) with ZVT drop (a combined formulation ofmultivitamin-multimineral, flaxseed oil, and lysine) at the dose of 25 and 50 mg/kg/day for 45 days. Hematological and immunological parameters,such as immunoglobulin (Ig)G, IgM, interferon-γ, interleukin-2, and interleukin-4, were assessed. In addition, histopathological examination of thespleen was also performed.Results: There were no significant changes in all the hematological parameters such as total leukocyte, differential leukocyte, total erythrocyte, andtotal platelets count, hemoglobin amount and also the immunological parameters such as IgG, IgM, interferon-γ, and interleukin-4 level among thetreatment groups except interleukin-2. There was a significant increase in interleukin-2 level in the group of animals treated with ZVT drop at the doseof 25 mg/kg (p<0.001) and 50 mg/kg (p<0.05) in comparison with normal control animals.Conclusion: The present study revealed the immunomodulatory effect of ZVT drop at the dose of 25 and 50 mg/kg/day in normal healthy Wistar rats.Keywords: Zincovit drop, Flax seed oil, Multivitamin-multimineral nutritional food supplement, Cyclophosphamide, Immunomodulatory

INFLUENCE OF GENDER AND OBESITY ON ANALGESIC MODULATION OF TRAMADOL IN RATS

Objective: The objective of this study was to investigate the influence of gender and obesity on analgesic modulation of tramadol in Wistar rats.Methods: This study was carried out in two sets of experiments. In Set I experiment - 48 rats (body weight ≤150 g), 24 each male and female rats were randomly divided into two groups (n=6/group) (Group I - Control; 0.9% NaCl; 1 ml/kg/day i.p. and Group II - Tramadol 10 mg/kg/day i.p.) for each nociception model - plantar test and acetic acid-induced writhing test. The treatment duration was of 5 days. On the last day of treatment (i.e., on the 5th day), paw withdrawal latency (PWL) was assessed using plantar test, and writhing movements were observed following administration of 0.8% acetic acid; 10 ml/kg i.p. Set II experiment was repeated like Set I experiment among rest 48 high-fat diet-fed rats (body weight ≥300 g).Results: For both males and females, PWL was significantly decreased (p<0.05) in obese control groups compared to lean control groups. A number of writhing movements were significantly increased (p<0.01 for males and p<0.001 for females) in obese control groups compared to lean control groups. In tramadol-treated obese rats, PWL was significantly decreased (p<0.01 for males and p<0.05 for females), and number of writhing movements were significantly increased (p<0.01 for both males and females) in comparison with the tramadol-treated lean rats.Conclusion: The present study revealed that obese female rats experience more pain sensation to noxious stimuli compared to lean male rats and also the analgesic effect of tramadol is more pronounced in lean male rats compared to obese female rats

CORRELATION OF GENDER AND LEPTIN WITH ANALGESIC EFFECT OF TRAMADOL IN RATS

 Objective: The objective of the study was to investigate the correlation of gender and serum leptin level with analgesic modulation of tramadol in Wistar rats.Methods: A total of 48 Wistar rats (body weight 100–150 g), 24 each male and female Wistar rats were randomly divided into two groups (n=6/group) (Group I - Control- 0.9% NaCl; 1 ml/kg/day i.p. and Group II - Tramadol 10 mg/kg/day i.p.) for each nociception model - plantar test and acetic acid induced writhing test. The treatment duration was of 5 days. Paw withdrawal latency (PWL) was assessed using plantar test and writhing movements were observed following administration of 0.8% acetic acid; 10 ml/kg i.p.Results: PWL was significantly decreased (p<0.001) and both number of writhing movements and serum leptin concentrations were significantly increased (p<0.001) in female control group compared to male control group. In tramadol treated female rats, PWL was significantly decreased (p=0.005) and both number of writhing movements and serum leptin concentrations were significantly increased (p<0.001) in comparison with the tramadol treated male rats. PWL was negatively correlated with serum leptin concentration (Pearson correlation coefficient= −0.826, two-tailed significance= 0.000), and writhing movements were positively correlated with serum leptin concentration (Pearson correlation coefficient= 0.505, two-tailed significance= 0.012).Conclusions: The present study revealed that female rats have more serum leptin concentration than male rats which could be one of the possible reasons for having more pain sensitivity to noxious stimuli in female rats compared to male rats. Tramadol treatment at the dose of 10 mg/kg for 5 days has decreased serum leptin level in rats which might be one of the additional mechanisms of tramadol to reduce pain

EFFECT OF SODIUM VALPROATE AND DOCOSAHEXAENOIC ACID ON INFLAMMATION IN RATS

Objective: To evaluate the anti-inflammatory activity of sodium valproate and docosahexaenoic acid (DHA) supplementation using various experimental models in albino Wistar rats.Method: A total of 48 adult Wistar albino male rats were divided into 8 groups of 6 rats each. Group I was control (distilled water 1 ml/kg), Group II received intraperitoneal (i.p.) injection of indomethacin (10 mg/kg), Groups III-V were injected (i.p.) with sodium valproate 100, 200, and 400 mg/kg water, and Groups VI-VIII were given sodium valproate 100, 200, and 400 mg/kg plus DHA 300 mg/kg (i.p.), respectively. Anti-inflammatory activity was assessed using carrageenan induced paw edema and the cotton pellet granuloma models.Results: We found that higher doses of sodium valproate (400 mg/kg) used either alone or with a combination of DHA (300 mg/kg) showed a significant anti-inflammatory activity when compared to control in both the models of inflammation.Conclusion: Combination of sodium valproate along DHA has shown promising anti-inflammatory activity.Keywords: Anti-inflammatory drugs, Sodium valproate, Rat model

AMELIORATIVE EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS AGAINST SCOPOLAMINE-INDUCED MEMORY IMPAIRMENT IN RATS

ABSTRACTObjective: The present study was designed to investigate the cognitive enhancing property of angiotensin receptor blockers (ARBs) in scopolamineinducedamnesic rats.Methods: A total of 42 male Wistar rats were divided into seven groups. Group 1 received 2% gum acacia orally for 4 weeks, Group 2 received normalsaline, and Group 3 received scopolamine (2 mg/kg/i.p.) as a single dose. Groups 4 and 5 received telmisartan (1.80 mg/kg and 3.60 mg/kg, respectively)while Groups 6 and 7 received losartan (2.25 mg/kg and 4.50 mg/kg, respectively), orally for 4 weeks, followed by scopolamine (2 mg/kg/i.p.) given45 minutes prior to experimental procedure. Evaluation of learning and memory was assessed by using morris water maze test followed by estimationof hippocampal choline acetyltransferase (ChAT) activity. Alterations in hippocampal morphology and degree of neuronal survival were also analyzedfollowing drug treatments.Results: Scopolamine-induced marked impairment of memory in the behavioral test which correlated with reduced ChAT activity and morphologicalchanges in the hippocampus. Treatment with higher doses of telmisartan and losartan improved memory deficits in scopolamine-induced amnesicrats while increasing the hippocampal ChAT activity. The treatments also attenuated hippocampal degeneration and increased the number of survivingneurons in hippocampus scopolamine-induced amnesic rats.Conclusion: Pre-treatment with ARBs attenuated scopolamine-induced memory deficits which may be attributed to their angiotensin receptorblockade property or to improved cholinergic activity, and thus highlighting the potential of these drugs in dementia.Keywords: Angiotensin scopolamine, Amnesia, Angiotensin receptor blockers, Losartan, telmisarta

Comparison of microvascular endothelial function as measured by laser Doppler flowmeter among non-smoker and smoker males

Background: To understand the role of smoking in influencing endothelial function as assessed by LDF among non-smoker and smoker males. Methods: The LDF measurement for a total of 35 non-smokers and 16 smokers was done in the central research laboratory after written informed consent. The change in LDF signal in response to acetylcholine 100 µl, which was delivered to the forearm skin by iontophoresis, was measured as perfusion units (PU). Results: The pre-ACh LDF signal were statistically not significant between the groups. The increase in LDF signal was more prominent in non-smoker group. The LDF signal parameters such as differences in minimal response pre and post-ACh; difference in mean response pre and post ACh; the difference in maximal response pre and post ACh was not statistically significant between groups. However, the difference in the area under curve (AUC) pre and post-ACh (PU.min) (non-smoker 20089.34 (3438.92) vs smoker 13220.72 (3379.52); p=0.16) showed a trend towards statistical significance. Conclusions: Microvascular endothelial function as assessed by LDF signal among smokers (pack-years;1.9±1.44) and non-smokers is statistically insignificant. However, lower microvascular endothelial function is observed among smokers

INFLUENCE OF TOPICAL RETAPAMULIN (1%) OINTMENT, SOFINOX- RD CREAM, SOFINOX CREAM (2%), ZINC FUSIDATE CREAM (2%) AND ZINC FUSIDATE OINTMENT (2%) ON NASAL MUCOSAL SURFACE SAFETY IN NEW ZEALAND ALBINO RABBITS

Objective: To investigate the comparative safety of Retapamulin 1% ointment, Sodium fusidate 0.25%, Sofinox 2% cream, Zinc fusidate 2% cream and Zinc fusidate 2% ointment on nasal mucosal surface in rabbits.Methods: In the experiment a total of 30 adult New Zealand albino rabbits of either sex were used. The rabbits were divided into five groups of six rabbits each. A thin layer of the drug was applied in the right nostril and left nostril was kept as control (no treatment) to their corresponding treatment group. Nasal safety of these drugs was assessed with the help of a symptom scoring system and photographic observations.Results: There was significant decrease of nasal rubbing (Rhinocnesmus) behaviors in experimental animals of Sofinox RD cream (p<0.001), Sofinox 2% cream (p<0.001), Zinc fusidate cream (p<0.001) and Zinc fusidate ointment (p<0.001) treated groups when compared with Retapamulin 1% ointment treated group. More redness was observed in nasal mucosal surface of both nostrils (Right nostril- Retapamulin 1% ointment, Left nostril- Control) of Retapamulin group animals in comparison with Sofinox RD cream, Sofinox 2% cream, Zinc fusidate 2% cream and Zinc fusidate 2% ointment group animals.Conclusion: In the present study, the comparative safety of test drugs on nasal mucosal surface of rabbits were found as- Zinc fusidate ointment > Zinc fusidate cream > Sofinox RD cream ~ Sofinox 2% cream > Retapamulin 1% ointment. Further, clinical evaluation has to be performed to precisely define the safety of Zinc fusidate ointment, Zinc fusidate cream, Sofinox RD cream and Sofinox 2% cream on nasal mucosal surface of human subjects.Â

Antiretroviral therapy outcome in human immuno-deficiency virus infected patients in a tertiary care hospital

Background: Human immunodeficiency virus (HIV) presently accounts for the highest number of deaths due to any infective agent in the world. The present study assessed the one year treatment outcome following antiretroviral therapy in HIV positive, treatment naïve patients in a tertiary care hospital.Methods: Adult HIV positive, antiretroviral treatment naive patients who were started on antiretroviral therapy (ART) between 1st January 2011 and 31st May 2013 were included in the study. Data was collected from their case records. CD4+cell count, haemoglobin level, weight, occurrence of opportunistic infections (OIs) and adverse drug reactions (ADRs) were analysed at baseline, 6 and 12 months following start of antiretroviral therapy. Data was analysed using parametric and nonparametric tests.Results: Data of 325 patients was analysed. Overall, the median increase in CD4+ count at 1 year after initiation of treatment was observed to be clinically significant. Patients on tenofovir based regimen showed a significantly greater increase in the median CD4+ count (P = 1.12×10-05) and haemoglobin (P = 0.002) as compared to those on non-tenofovir based regimen. A total of 151 ADRs were recorded in the study, of which the most common were skin rash 24%, anaemia and gastrointestinal side effects 17% each. Frequency of opportunistic infections gradually declined after ART. At the end of 1 year of treatment, the cumulative loss to follow up was 7.4%.Conclusions: By following the current national guidelines, the desired immunological and clinical response following initiation of ART can be achieved while minimizing drug toxicity

Neuronutraceuticals Combating Neuroinflammaging: Molecular Insights and Translational Challenges—A Systematic Review

Neuropathologies, such as neuroinflammaging, have arisen as a serious concern for preserving the quality of life due to the global increase in neurodegenerative illnesses. Nowadays, neuronutraceuticals have gained remarkable attention. It is necessary to investigate the bioavailability, off-target effects, and mechanism of action of neuronutraceuticals. To comprehend the comprehensive impact on brain health, well-designed randomized controlled trials testing combinations of neuronutraceuticals are also necessary. Although there is a translational gap between basic and clinical research, the present knowledge of the molecular perspectives of neuroinflammaging and neuronutraceuticals may be able to slow down brain aging and to enhance cognitive performance. The present review also highlights the key emergent issues, such as regulatory and scientific concerns of neuronutraceuticals, including bioavailability, formulation, blood–brain permeability, safety, and efficacy