Intrastriatal malonate administration induces convulsive behaviour in rats.
Malonic acidaemia is an inborn error of metabolism that accumulates malonate, a competitive succinate dehydrogenase (SDH; EC 1.3.99.1) inhibitor. The present study investigated the behavioural effects of unilateral intrastriatal administration of malonate (0.6, 1.8 or 6 micromol) in adult male Wistar rats (n=10-13). Low doses of malonate (1.8 micromol) decreased exploratory activity and caused ipsiversive rotational behaviour. High doses of malonate (6 micromol) induced contralateral rotational behaviour and convulsive episodes. Malonate competitively inhibited SDH in mitochondrion-enriched fractions from striatum ( Ki=0.034+/-0.008 mmol/L). Interestingly, methylmalonate, which is a weaker SDH inhibitor than malonate (Ki=4.22+/-1.3 mmol/L), induced more convulsions than malonate at equimolar doses and did not cause ipsiversive rotational behaviour. It is suggested that the potency of SDH inhibition in vitro does not correlate positively with the convulsant potential of these inhibitors in vivo.
Fleck
J
J
Centro Universitário Franciscano, Santa Maria, RS, Brazil.
Ribeiro
M C P
MC
Schneider
C M
CM
Sinhorin
V D G
VD
Rubin
M A
MA
Mello
C F
CF
D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology*; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D008845:Microinjections; D051381:Rats; D017208:Rats, Wistar
D008314:Malonates; C030290:malonic acid