Sousa Karen, Decker Natalia, Pires Thienne Rocha, Papke Débora Kuck Mausolff, Coelho Vanessa Rodrigues, Pflüger Pricila, Pereira Patrícia, Picada Jaqueline Nascimento
Laboratory of Toxicological Genetics, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, Canoas, RS, 2425-900, Brazil.
Laboratory of Neuropharmacology and Pre-Clinical Toxicology. Pharmacology Department, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), Sarmento Leite Street, 500/305, Porto Alegre, RS, 90050-170, Brazil.
Psychopharmacology (Berl). 2017 Jan;234(1):129-136. doi: 10.1007/s00213-016-4446-z. Epub 2016 Sep 27.
Vigabatrin (VGB) is a drug indicated mostly for the treatment of spasms in childhood and West's syndrome patients. This drug inhibits irreversibly the enzyme GABA-transaminase (GABA-T), increasing GABA concentrations and enhancing GABAergic neurotransmission in the brain, which is known to induce behavioral changes.
The aims of this study were to evaluate the effects of VGB in the short-term memory (STM), long-term memory (LTM), motivation, locomotion, and exploratory behavior tests and to detect deleterious or protective effects on DNA in target tissues of the drug.
Male Wistar rats were treated with a single dose of VGB (100, 250, or 500 mg/kg) or saline solution before the inhibitory avoidance and open-field tasks. DNA damage was evaluated using the alkaline comet assay in peripheral blood, cerebral cortex, and hippocampus after behavioral testing.
There was no significant difference in the inhibitory avoidance task between the treated groups and the saline group. In all tested doses, VGB reduced the number of rearings in the open-field task. Besides, VGB 500 mg/kg affected locomotion, though it was not able to induce any DNA damage.
VGB did not affect STM and LTM, but the drug impaired the exploration and locomotion likely associated with its sedative effect. In addition, no DNA damage in cortex and hippocampus was detected after behavioral testing, when brain GABA levels are already increased.
氨己烯酸（VGB）是一种主要用于治疗儿童痉挛和韦斯特综合征患者的药物。该药物不可逆地抑制γ-氨基丁酸转氨酶（GABA-T），增加γ-氨基丁酸（GABA）浓度并增强大脑中的GABA能神经传递，已知这会引起行为变化。
本研究的目的是评估VGB在短期记忆（STM）、长期记忆（LTM）、动机、运动和探索行为测试中的作用，并检测该药物对靶组织DNA的有害或保护作用。
在抑制性回避和旷场试验前，给雄性Wistar大鼠单次注射VGB（100、250或500mg/kg）或生理盐水。行为测试后，使用碱性彗星试验评估外周血、大脑皮层和海马体中的DNA损伤。
治疗组与生理盐水组在抑制性回避任务上无显著差异。在所有测试剂量下，VGB均减少了旷场试验中的直立次数。此外，500mg/kg的VGB影响运动，但未引起任何DNA损伤。
VGB不影响STM和LTM，但该药物可能因其镇静作用而损害探索和运动能力。此外，行为测试后，在大脑GABA水平已经升高时，未检测到皮层和海马体中的DNA损伤。
