THE AIM OF THE STUDY: To investigate the effects of the chronic (28 days) oral administration of CT root extract on CCH-induced cognitive impairment, neuronal damage and cholinergic deficit, and its toxicity profile in the CCH rat model.
MATERIALS AND METHODS: The permanent bilateral occlusion of common carotid arteries (PBOCCA) surgery method was employed to develop a CCH model in male Sprague Dawley (SD) rats. Then, these rats were given oral administration of CT root extract at doses of 100, 200, and 300 mg/kg, respectively for 28 days and subjected to behavioural tests. At the end of the experiment, the brain was harvested for histological analysis and cholinesterase activities. Then, blood samples were collected and organs such as liver, kidney, lung, heart, and spleen were procured for toxicity assessment.
RESULTS: Chronic treatment of CT root extract at doses of 200 and 300 mg/kg, restored memory impairments induced by CCH. CT root extract was also found to diminish CCH-induced neuronal damage in the CA1 region of the hippocampus. High dose (300 mg/kg) of the CT root extract was significantly inhibited the increased acetylcholinesterase (AChE) activity in the frontal cortex and hippocampus of the PBOCCA rats. In toxicity study, repeated doses of CT root extract were found to be safe in PBOCCA rats after 28 days of treatment.
CONCLUSIONS: Our findings provided scientific evidence supporting the therapeutic potential of CT root extract in the treatment of vascular dementia (VaD)-related cholinergic abnormalities and subsequent cognitive decline.
METHODS: Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platform condition for 72 hr. During this procedure, saline or nicotine (1 mg/kg) was given subcutaneously twice a day. Then, Morris water maze (MWM) test was used to assess learning and memory performance of the rats. The rats were sacrificed and the brain was harvested for immunohistochemistry and Western blot analysis.
RESULTS: MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein.
CONCLUSION: This study suggests that changes in DREAM protein expression in CA1, CA2, CA3, and DG regions of rat's hippocampus and mean relative level of DREAM protein may involve in the mechanism of nicotine treatment-prevented REM sleep deprivation-induced learning and memory impairment in rats.
MATERIALS AND METHODS: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl's staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes.
RESULTS: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil.
CONCLUSION: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.
OBJECTIVES: The present study was performed to investigate the discriminative stimulus effects of MG in rats. The pharmacological mechanism of MG action and its derivative, 7-hydroxymitragynine (7-HMG) with a specific focus on opioid receptor involvement was examined in rats trained to discriminate morphine from vehicle. In order to study the dual actions of MG, the effect of cocaine substitution to the MG discriminative stimulus was also performed in MG-trained rats.
METHODS: Male Sprague Dawley rats were trained to discriminate MG from vehicle in a two-lever drug discrimination procedure under a tandem variable-interval (VI 60') fixed-ratio (FR 10) schedule of food reinforcement.
RESULTS: Rats acquired the MG discrimination (15.0 mg/kg, i.p.) which was similar to the acquisition of morphine discrimination (5.0 mg/kg, i.p.) in another group of rats. MG substituted fully to the morphine discriminative stimulus in a dose-dependent manner, suggesting pharmacological similarities between the two drugs. The administration of 7-HMG derivative in 3.0 mg/kg (i.p.) dose engendered full generalisation to the morphine discriminative stimulus. In addition, the MG stimulus also partially generalised to cocaine (10.0 mg/kg, i.p.) stimulus.
CONCLUSION: The present study demonstrates that the discriminative stimulus effect of MG possesses both opioid- and psychostimulant-like subjective effects.
MATERIALS AND METHODS: 21 day postnatal male Sprague Dawley rats were assigned as Normal control [NC] fed normal chow diet, Obesity-induced [OB] fed high fat diet, Obesity-induced fed choline & DHA [OB + CHO + DHA], Obesity-induced environmental enrichment [OB + EE] [n = 8/group]. Memory was assessed using radial arm maze. Subsequently blood was collected for serum lipid analysis and rats were euthanized. 5 µm hippocampal sections were processed for cresyl-violet stain. Surviving neural cells were counted using 100 µm scale.
RESULTS: Memory errors were significantly higher [p
OBJECTIVE: To investigate cognitive mechanisms associated with decision-making in youths with OCD by using executive functioning tasks and computational modeling.
DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 50 youths with OCD (patients) and 53 healthy participants (controls) completed a probabilistic reversal learning (PRL) task between January 2014 and March 2020. A separate sample of 27 patients and 46 controls completed the Wisconsin Card Sorting Task (WCST) between January 2018 and November 2020. The study took place at the University of Cambridge in the UK.
MAIN OUTCOMES AND MEASURES: Decision-making mechanisms were studied by fitting hierarchical bayesian reinforcement learning models to the 2 data sets and comparing model parameters between participant groups. Model parameters included reward and punishment learning rates (feedback sensitivity), reinforcement sensitivity and decision consistency (exploitation), and stickiness (perseveration). Associations of receipt of serotonergic medication with performance were assessed.
RESULTS: In total, 50 patients (29 female patients [58%]; median age, 16.6 years [IQR, 15.3-18.0 years]) and 53 controls (30 female participants [57%]; median age, 16.4 years [IQR, 14.8-18.0 years]) completed the PRL task. A total of 27 patients (18 female patients [67%]; median age, 16.1 years [IQR, 15.2-17.2 years]) and 46 controls (28 female participants [61%]; median age, 17.2 [IQR, 16.3-17.6 years]) completed the WCST. During the reversal phase of the PRL task, patients made fewer correct responses (mean [SD] proportion: 0.83 [0.16] for controls and 0.61 [0.31] for patients; 95% CI, -1.31 to -0.64) and switched choices more often following false-negative feedback (mean [SD] proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients; 95% CI, 0.60-1.26) and true-positive feedback (mean [SD] proportion: 0.93 [0.17] for controls vs 0.73 [0.34] for patients; 95% CI, -2.17 to -1.31). Computational modeling revealed that patients displayed enhanced reward learning rates (mean difference [MD], 0.21; 95% highest density interval [HDI], 0.04-0.38) but decreased punishment learning rates (MD, -0.29; 95% HDI, -0.39 to -0.18), reinforcement sensitivity (MD, -4.91; 95% HDI, -9.38 to -1.12), and stickiness (MD, -0.35; 95% HDI, -0.57 to -0.11) compared with controls. There were no group differences on standard WCST measures and computational model parameters. However, patients who received serotonergic medication showed slower response times (mean [SD], 1420.49 [279.71] milliseconds for controls, 1471.42 [212.81] milliseconds for patients who were unmedicated, and 1738.25 [349.23] milliseconds for patients who were medicated) (control vs medicated MD, -320.26 [95% CI, -547.00 to -88.68]) and increased unique errors (mean [SD] proportion: 0.001 [0.004] for controls, 0.002 [0.004] for patients who were unmedicated, and 0.008 [0.01] for patients who were medicated) (control vs medicated MD, -0.007 [95% CI, -3.14 to -0.36]) on the WCST.
CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study indicated that youths with OCD showed atypical probabilistic reversal learning but were generally unimpaired on the deterministic WCST, although unexpected results were observed for patients receiving serotonergic medication. These findings have implications for reframing the understanding of early-onset OCD as a disorder in which decision-making is associated with uncertainty in the environment, a potential target for therapeutic treatment. These results provide continuity with findings in adults with OCD.