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1.
Hum Exp Toxicol ; 35(9): 958-65, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26500220

ABSTRACT

Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group.


Subject(s)
4-Aminobutyrate Transaminase/antagonists & inhibitors , Anticonvulsants/toxicity , DNA Damage , Micronuclei, Chromosome-Defective/chemically induced , Vigabatrin/toxicity , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/enzymology , Cerebral Cortex/pathology , Comet Assay , Dose-Response Relationship, Drug , Hippocampus/drug effects , Hippocampus/enzymology , Hippocampus/pathology , Liver/drug effects , Liver/enzymology , Liver/pathology , Male , Micronucleus Tests , Motor Activity/drug effects , Organ Specificity , Rats, Wistar , Rotarod Performance Test , Time Factors
2.
Phytomedicine ; 18(10): 896-901, 2011 Jul 15.
Article in English | MEDLINE | ID: mdl-21420842

ABSTRACT

It is known that (-)-linalool is a competitive antagonist of NMDA receptors, which play a key role in the learning and memory processes; however, only a few studies have reported a possible interference of (-)-linalool in memory. The purpose of this study was to investigate the (-)-linalool effects on acquisition of short- and long-term memories through the objects recognition task, inhibitory avoidance test and habituation to a novel environment. Furthermore, the open field test was used to investigate the interference of (-)-linalool in motivation, locomotion and exploration by animals. Wistar male adult rats received an intraperitoneal injection (i.p.) of saline (NaCl 0.9%), tween 5% or (-)-linalool (50 or 100 mg/kg) before training in the tasks; MK-801 (0.1 mg/kg), a glutamate antagonist, was used as positive control. Short-term (STM) and long-term (LTM) memories were tested 1.5 and 24 h after training, respectively, in the inhibitory avoidance and recognition objects. The results suggested that (-)-linalool (as 50- and 100-mg/kg doses) impaired LTM acquisition, but not STM acquisition, in the object recognition task. In the inhibitory avoidance test, animals receiving linalool (both doses) showed impairment in acquisition of both memories measured. In the open field test, the animals that received (-)-linalool showed no significant difference in the crossings and latency to start the locomotion in any of the doses tested, although (-)-linalool 100 mg/kg reduced rearing behavior. When re-exposed to open field 24 h after training, the rats that received (-)-linalool 100mg/kg showed no habituation. Taken together, these data suggested that (-)-linalool was able to impair the acquisition of memory in rats, which can be associated to (-)-linalool antagonist capacity as regards NMDA glutamatergic receptors, since other glutamate antagonists also seem to affect memory.


Subject(s)
Avoidance Learning/drug effects , Habituation, Psychophysiologic/drug effects , Memory/drug effects , Monoterpenes/pharmacology , Acyclic Monoterpenes , Analysis of Variance , Animals , Dizocilpine Maleate/pharmacology , Inhibition, Psychological , Male , Monoterpenes/administration & dosage , Plant Preparations/pharmacology , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
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