Fig. 3: Behavioral consequences of in vivo rotenone-induced mild mitochondrial dysfunction in mice and their reversal by lithium treatment.

0.75 mg/kg/day rotenone (Rot.) was administered i.p. for 4 or 8 weeks. Lithium (Li) was given for the last 2 weeks of rotenone treatment. Results represent means ± SEM of three independent experiments with at least three mice/group in each experiment. In each test (EPM, FST and amphetamine-induced hyperlocomotion) one result exceeding ±2SDs was excluded. A The effect on the behavior in the EPM. Time in the open arms/total time was increased by Rot. following 4 weeks and reduced following 8 weeks of treatment. Three-way ANOVA with treatment (± Rot.), Li (±) and duration of treatment (4/8 weeks) as main factors: ^#values are of the TreatmentXLiXDuration interaction; *Fisher’s LSD post hoc test: 4/8 weeks Rot. or Li vs. vehicle and vs. Rot.+Li, p < 0.04. B The effect on the behavior (immobility time) in the FST. Three-way ANOVA with treatment (± Rot.), Li (±) and duration of treatment (4/8 weeks) as main factors: ^#values are of the TreatmentXLiXDuration interaction; *Fisher’s LSD post hoc test: 4/8 weeks Rot. vs. vehicle and vs. Rot.+Li, p < 0.03. C The effect in the amphetamine-induced hyperlocomotion paradigm. Ci. Repeated measures ANOVA of the results following amphetamine injection revealed that Rot. significantly augmented the effect of amphetamine (^#Fisher’s LSD post hoc test, p < 0.03). Li by itself significantly reversed amphetamine’s effect (**p ≤ 0.03) and totally reversed the effect of Rot. on amphetamine-induced hyperlocomotion (*p < 0.003). Cii. Repeated measures ANOVA of the results following amphetamine treatment revealed that Li by itself significantly reversed amphetamine’s effect (**p ≤ 0.05) and totally abolished amphetamine-induced hyperlocomotion (*p < 0.0001).