Microdialysis study of striatal dopamine in MPTP-hemilesioned rats challenged with apomorphine and amphetamine

Abstract: Motor impairments of Parkinson''s disease (PD) appear only after the loss of more than 70% of the DAergic neurons of the substantia nigra pars compacta (SNc). An earlier phase of this disease can be modeled in rats that received a unilateral infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) into the SNc. Though these animals do not present gross motor impairments, they rotate towards the lesioned side when challenged with DAergic drugs, like amphetamine and apomorphine. The present study aimed to test whether these effects occur because the drugs disrupt compensatory mechanisms that keep extracellular levels of dopamine in the striatum (DAE) unchanged. This hypothesis was tested by an in vivo microdialysis study in awake rats with two probes implanted in the right and left striatum. Undrugged rats did not present turning behaviour and their basal DAE did not differ between the lesioned and sham-lesioned sides. However, after apomorphine treatment, DAE decreased in both sides, but to a larger extent in the lesioned side at the time the animals started ipsiversive turning behaviour. After amphetamine challenge, DAE increased in both sides, becoming significantly higher in the non-lesioned side at the time the animals started ipsiversive turning behaviour. These results are in agreement with the hypothesis that absence of gross motor impairments in this rat model of early phase PD depends on maintenance of extracellular DA by mechanisms that may be disrupted by events demanding its alteration to higher or lower levels. [Copyright &y& Elsevier]