Genetic differences in the effects of delta-aminolevulinic acid on seizure latency in mice.
delta-Aminolevulinic acid, an intermediate in heme formation, is elevated in certain human disorders including acute intermittent porphyria, tyrosinemia, and lead poisoning. It has been implicated in the central nervous system manifestations of these disorders via interactions with the GABAergic system. This potential interaction was examined by testing whether or not delta-aminolevulinic acid could alter the latency to seizure in mice. Seizures were induced in a variety of inbred strains of mice including C57BL, C3H, DBA mice and in a heterogeneous stock of mice. Flurothyl and 3-mercaptopropionic acid were used to induce seizures in the presence and absence of delta-aminolevulinic acid administered either i.p. (0.5 and 1.5 mmol/kg), or i.c.v. (4.5 and 450 nmol). delta-Aminolevulinic acid increased the latency to myoclonic and clonic seizures induced by flurothyl when administered i.p.; i.c.v. injections also delayed clonic seizures induced by flurothyl, and increased the latency to tonic seizures induced by 3-mercaptopropionic acid. The degree to which delta-aminolevulinic acid altered seizure latency in all tests was dependent on strain of mouse tested. These data support the conclusion that delta-aminolevulinic acid can act as an anticonvulsant agent, and mimic the effects of GABA. Moreover, there is genetic variation in the sensitivity of the various strains of mice to delta-aminolevulinic acid.
D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D007274:Injections, Intraperitoneal; D007982:Levulinic Acids / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007982:Levulinic Acids; D005680:gamma-Aminobutyric Acid; D000622:Aminolevulinic Acid