Cognitive, motor and tyrosine hydroxylase temporal impairment in a model of parkinsonism induced by reserpine

Abstract Studies have suggested that cognitive deficits can precede motor alterations in Parkinson's disease (PD). However, in general, classic animal models are based on severe motor impairment after one single administration of neurotoxins, and thereby do not express the progressive nature of the pathology. A previous study showed that the repeated administration with a low dose (0.1 mg/kg) of the monoamine depleting agent reserpine induces a gradual appearance of motor signs of pharmacological parkinsonism in rats. Here, we showed this repeated treatment with reserpine induced a memory impairment (evaluated by the novel object recognition task) before the gradual appearance of the motor signs. Additionally, these alterations were accompanied by decreased tyrosine hydroxylase (TH) striatal levels and reduced number of TH+ cells in substantia nigra pars compacta (SNpc). After 30 days without treatment, reserpine-treated animals showed normal levels of striatal TH, partial recovery of TH+ cells in SNpc, recovery of motor function, but not reversal of the memory impairment. Furthermore, the motor alterations were statistically correlated with decreased TH levels (GD, CA1, PFC and DS) and number of TH+ cells (SNpc and VTA) in the brain. Thus, we extended previous results showing that the gradual appearance of motor impairment induced by repeated treatment with a low dose of reserpine is preceded by short-term memory impairment, as well as accompanied by neurochemical alterations compatible with the pathology of PD.