Celastrus paniculatus and memantine prevent alcohol dependence and improve decision making in alcohol dependent C57BL6 mice

Background: Alcohol use disorder poses a huge burden with only a handful of approved drugs. AUD is associated with impaired decision-making that leads to compulsive drinking despite negative consequences. A drug that decreases alcohol consumption as well as improves decision-making may thus prove more useful. This study was planned to evaluate the effect of two drugs, Celastrus paniculatus and memantine on alcohol preference and decision impairment in alcohol-dependent mice. Methods: In part 1, the effect of both the study drugs on alcohol consumption was studied using intermittent access model in 70 male C57BL6 mice. In part 2, effect of drugs on decision making was studied using the rodent version of Iowa gambling task. Mice were divided in seven study groups: Group 1-3: Celastrus paniculatus (140, 280, and 560 mg/kg), Group 4: memantine (25 mg/kg), Group 5: vehicle control 1 (Milk), Group 6: vehicle control 2 (normal saline) and Group 7: naltrexone(1mg/kg). Results: Percentage alcohol preference was lower in test groups i.e., Celastrus paniculatus at medium (40.90±15.18%) and high doses (31.79±7.46%) vs. milk (82.74±8.53%; p<0.05); and in memantine group (36.28±10.99%) vs. normal saline (83.27±5.51%; p<0.05). The results were not significantly different to Naltrexone (19.70±6.90%). Percentage preference to disadvantageous arms was also lower in Celastrus paniculatus, at medium (50.52±1.92%) and high doses (48.11±2.43%) compared to milk (54.47±2.73%; p<0.05) and memantine (47.45±1.67%) compared to normal saline (54.00±2.73%; p<0.05), indicating better decision-making ability in the test groups. The findings were comparable to Naltrexone group (45.43±2.52%). Conclusions: These results indicate that Celastrus paniculatus and memantine reduce alcohol consumption and improve decision making in alcohol-dependent mice.

Effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on ADP-induced platelet aggregation.

A randomized, observer-blind, parallel-group study was carried out to compare the effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on platelet aggregation, measured at a time expected to coincide with trough plasma levels of these drugs. 24 patients (age-30 to 60 yrs) with uncomplicated mild to moderate hypertension who completed a placebo run-in phase successfully were recruited in this study. They were randomly allocated to one of the 4 treatments: prazosin GITS 2.5 mg OD (Group 1), atenolol 50 mg OD (Group II), nifedipine SR 20 mg BD (Group III), and enalapril 5 mg OD (Group IV). All the drugs were given for 7 days, and blood samples were collected at 0 hr on day 1 (pre-treatment) and day 8 (post-treatment). Based on the dose (incremental concentrations of ADP)--response (% maximum aggregation) curve obtained, 2.5 microM/L of ADP was used to compare % inhibition of platelet aggregation among the 4 groups. We found that prazosin GITS inhibited % maximum aggregation significantly (p = 0.02) at 2.5 microM/L of ADP. Such inhibitory effect was not seen in any of the other groups. The inhibition produced by prazosin GITS differed significantly from the action of the other 3 drugs (p < 0.05). This antiplatelet effect of prazosin GITS bears more clinical relevance in view of the fact that it was seen at a time which is expected to coincide with the trough plasma levels of prazosin.

Effect of induction-delivery and uterine-delivery on apgar scoring of the newborn.

Very short or prolonged induction-delivery interval (i.e. less than 5 minutes or more than 15 minutes) and uterine-delivery interval of more than 90 seconds has a definite effect on the apgar scoring of a newborn especially when general anaesthesia is administered as compared to regional anaesthesia for caesarean section.