George Jîtcă1,2, Zsolt Gáll1, Camil E Vari1, Bianca E Ősz1, Amelia Tero-Vescan3, Alexandra Groșan1, Maria T. Dogaru1
1. Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Doctoral School of Medicine and Pharmacy, I.O.S.U.D., George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Department of Biochemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
Objective: One of the most common side effects of haloperidol is the extrapyramidal syndrome, resulting from inhibition of nigrostriatal dopaminergic circuits and mitochondrial dysfunction due to structural similarities to pyridinium derivative, MPP+ that induce oxidative stress. In exchange, the use of metformin appears to enhance neurogenesis, energy metabolism, and oxidative status, so these properties can be speculated in the context of drug-induced pseudoparkinsonism by haloperidol.
Methods: To assess motor coordination and activity, rodents were divided into four groups: CTR (n = 10) – animals that received distilled water, METF (n = 10) – animals that received metformin 500 mg / kgbw, HAL (n = 10) – animals that received haloperidol 2mg / kgbw, HALMETF (n = 10) – haloperidol 2mg / kgbw and metformin 500 mg / kgbw. The treatment was administered for 34 days at the same time by gastric gavage, during which time behavioral tests, rotarod (days 7, 14, 21, 28), catalepsy (day 30), open field (day 32) and novel object recognition (day 34) were performed.
Results: The monitored parameters, showed significant differences between the groups of interest (HAL and HALMETF respectively), so that the administration of metformin at the beginning of treatment reduces the cataleptic behavior. The HALMETF group shows an attenuation of the motor deficit during the rotarod test and the freezing period from the Open Field test, is diminished.
Conclusions: Metformin treatment has a beneficial effect in haloperidol-treated rats, demonstrated by decreased cataleptic behavior, improved motor performance and reduced haloperidol-induced anxiety behavior.
George Jîtcă, Bianca-Eugenia Ősz, Szende Vancea, Amalia Miklos, Amelia Tero-Vescan
University of Medicine and Pharmacy of Tîrgu Mureș, Romania
Objective: The purpose of this study was to develop a LC-MS method to determine amiodarone (AMI) and its major metabolite desethylamiodarone (DEA) from rat plasma released from the adipose tissue of AMI treated rats subjected to a weight gain/weight loss cycle.
Methods: Separation of the compounds was performed on a Kinetex 2.6 μm C18 100 x 4.6 mm column under isocratic conditions using a mixture of acetonitrile: 0.1% formic acid 65:35 at a flow rate of 0.5 ml/min. Detection of the analyte was performed by electrospray positive ionization, the monitored ions being 135 m/z from 646 for AMI and 135 m/z of 618 for DEA. Analytes were extracted after plasma protein precipitation with methanol.
Results: The developed method presented specificity and linearity on the concentration range of 25-2500 ng/ml plasma for AMI and 2.5-1250 ng/ml plasma for DEA and the precision and accuracy of the method at all of quality control concentration levels including LLOQ were according to official guidelines for validating analytical methods.
Conclusions: A sensitive and accurate LC-MS method has been developed with a much lower LLOQ than literature data to detect the plasma concentration differences of the studied analytes that result from forced lipolysis and mobilization from the adipose tissue.
University of Medicine and Pharmacy Tirgu Mures, Romania
Objective: To investigate the effect of anesthesia on rats’ ability of learning and over their impulsivity.
Material and Methods: We studied eight Wistar adult male rats, test and drug naive subjects. Animals were separated in two groups, group A and B with four members each. Group A included the anesthetized animals. The combination of ketamine, xylazine and piplophen in 2ml/kg body weight dosage was used and testing was done 24 hours after anesthesia. Group B was taken as control. The study was conducted using the ”Delay discounting” apparatus. Experiments assessing impulsive behavior were conducted using automated operant chambers, equipped with two nose-poke holes (holes where pellets of food were released). Rat’s answer was considered touching the nose-poke hole. One answer was rewarded with pellets of food of 45 mg each (small reward), while another hole released five pellets of 45 mg each (high reward). Both types of rewards were presented immediately after rat’s answer and were followed for a period of 25 seconds timeout. During the training phase, rats were placed in operant chambers 30 minutes per day, 5 consecutive days. The growing percent of preference for greater reward indicates learning.For the testing phase the procedure was similar, but a delay was introduced before the release of the big reward. During this phase, the preference for higher reward was indicative for non-impulsive behaviour.
Results: The results didn’t show significant statistically differences between the two groups.
Conclusions: Anesthesia had no effect on learning ability nor on impulsivity.
The prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is very controversial. There is no conclusive evidence for increased risk of malformations after SSRI use in pregnancy. The aim of the study was to determine how fluoxetine is affecting gestation and fetal development in rats. Twenty sexually mature female Wistar rats weighting between 250-260 g received 20 mg/kg body weight fluoxetine from the first day of gestation and during the entire gestation period.The drug was administered by oral route. Healthy, primipareus animals were selected along with 20 female Wistar rats, as control group. Mature males were caged with virgin females for an entire week. Rat’s behaviour during gestation, after birth and rats body weight was examined. The number of healthy pups was also noted. The females not giving birth after 21 days to any pup were anesthetized (halothane through gas scavenging apparatus untilled death) and the gravid uterus were dissected out and examined. Compared to the controlled group, in which weight gain was more significant, the animals from the experimental group had a slight increase in body weight. The weight gain normally induced by gestation, is less significant in fluoxetine treated rats due to the increase serotonin levels in the brain. The uteri examination of pregnant rats showed an increase in the number of dead and resorbed rat embryos.
Preclinical studies suggest that the inclusion of fluoxetine in pregnancy category C is justified and the appropriateness of its administration in pregnancy is still an unresolved issue.
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