Cash, Diana

Hunter, A.J

Ireland, M D

Lowe, A.S.

Roberts, T J

Virley, D

Williams, Steven

The neurotoxin MPTP selectively destroys nigrostriatal dopaminergic pathways producing parkinsons-like lesions in primates and C57 mice. Unlike primates, MPTP-lesioned mice rarely exhibit robust behavioural deficits, limiting in vivo evaluation of the model. Here we compared amphetamine-induced changes in locomotion in lesioned mice against controls (5 mg/kg, sc, n=8 per group). Adult male C57 mice, treated with 4X10 mg/kg MPTP or saline (ip at hourly intervals), were tested in computerised activity measurement apparatus (Columbus Instruments, USA). Amphetamine-induced increase in locomotion was significantly higher in the lesioned than in the control group (increase over baseline, mean +- sd cm/90min, 14430 +- 3378 and 9314 +- 2638 respectively, p&lt;0.05). To detect brain regions involved in response to amphetamine, a separate cohort of 4 MPTP-treated mice and 4 controls underwent T2*-sensitive functional MRI study conducted in a 4.7T Varian imaging system. Anaesthetised mice were imaged for 30 min before and 60 min after amphetamine (5mg/kg, sc). Voxel-wise group statistical analysis (SPM99, Institute of Neurology, London, UK) detected significant amphetamine-induced BOLD contrast increases in the nucleus accumbens, septum, striatum and hypothalamus, and decreases in the hippocampus. Regions with BOLD increases were similar in both MPTP-treated and control group while there was a notable absence of hippocampal decrease in the MPTP-treated group. The results indicate that functional differences between the normal and lesioned mice, precipitated by amphetamine, may be further elucidated by fMR

Amphetamine-induced changes in normal and mptp-lesioned mice: a behavioural and fmri study

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