Behavioural and neurochemical response of α-synuclein A30P transgenic mice to the effects of L-DOPA

Transgenic mice carrying human A30P mutated alpha-synuclein demonstrate hypolocomotion and dysfunction of the presynaptic machinery of dopamine overflow, induced by reducing capacity of the dopamine storage pool. We suggested that overexpression of alpha-synuclein may change sensitivity of these mice to L-DOPA. Current study assessed behavioural and neurochemical responses in A30P mice to L-DOPA using automated activity monitoring and voltammetry. We confirmed decreased locomotion and rearing of A30P transgenic mice compared to wild-type controls. L-DOPA (10-200 mg/kg, i.p.) dose-dependently lowered locomotor activity, including stereotypy, in both genotypes, but the effects were larger in A30P mice. The effects of drug on stimulated dopamine overflow were investigated in the nucleus accumbens shell. L-DOPA at the dose of 30 mg/kg did not change peak dopamine overflow induced by 10 Hz stimulation of the medial forebrain bundle in either genotype, but increased it at the higher (20-50 Hz) frequencies of stimulation. At the higher frequencies of stimulation, L-DOPA elevated dopamine overflow significantly more in A30P mice than in the control animals. These data show that A30P transgenic mice are more sensitive to the effects of L-DOPA at both behavioural and neurochemical level. (C) 2008 Elsevier Ltd. All rights reserved.