Neurobehavioral effects of vigabatrin and its ability to induce DNA damage in brain cells after acute treatment in rats.
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.
Laboratory of Toxicological Genetics, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, Canoas, RS, 2425-900, Brazil.
Karen
K
Sousa
Laboratory of Toxicological Genetics, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, Canoas, RS, 2425-900, Brazil.
Natalia
N
Decker
Laboratory of Toxicological Genetics, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, Canoas, RS, 2425-900, Brazil.
Thienne Rocha
TR
Pires
Laboratory of Toxicological Genetics, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, Canoas, RS, 2425-900, Brazil.
Débora Kuck Mausolff
DK
Papke
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.
Vanessa Rodrigues
VR
Coelho
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.
Pricila
P
Pflüger
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.
Patrícia
P
Pereira
Laboratory of Toxicological Genetics, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, Canoas, RS, 2425-900, Brazil. jnpicada@gmail.com.
Jaqueline Nascimento
JN
Picada
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D009042:Motivation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020888:Vigabatrin / Q000494:pharmacology*
D000927:Anticonvulsants; D020888:Vigabatrin
Antiepileptic drug; GABA; Memory; Neuroprotection; Neurotoxicity
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