Energy metabolism is impaired in the Cu,Zn superoxide dismutase transgenic mouse model of amyotrophic lateral sclerosis. The goal was to investigate tolerance against single and repetitive hypoxia in C57BGSJL-TSN(SOD1-G93A)1GUR mice (G93A mice). Posthypoxic recovery (15 min hypoxia, 45 min recovery) of population spike amplitude in hippocampal region CA1 was 38 +/- 29% (mean +/- SD) in controls and 67 +/- 41% (ns) in G93A mice at day 40. Upon in vivo pretreatment with 20 mg/kg 3-nitropropionate posthypoxic recovery increased to 82 +/- 32% (P < 0.01) in controls and decreased to 35 +/- 33% in G93A mice (P < 0.05 to pretreated controls). Results at day 80 and 110 were similar. We conclude that G93A mice show a long-lasting impairment to sustain repetitive hypoxic episodes whereas tolerance to a single hypoxic episode is comparable to controls. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.