Animal models of early-stage Parkinson's disease and acute dopamine deficiency to study compensatory neurodegenerative mechanisms

Parkinson's disease is a common neurodegenerative disease characterized by a widely variety of motor and non-motor symptoms. While the motor deficits are only visible following a severe dopamine depletion, neurodegenerative process and some non-motor symptoms are manifested years before the motor deficits. Importantly, chronic degeneration of dopaminergic neurons leads to the development of compensatory mechanisms that play roles in the progression of the disease and the response to anti-parkinsonian therapies. The identification of these mechanisms will be of great importance for improving our understanding of factors with important contributions to the disease course and the underlying adaptive process. To date, most of the data obtained from animal models reflect the late, chronic, dopamine-depleted states, when compensatory mechanisms have already been established. Thus, adequate animal models with which researchers are able to dissect early- and late-phase mechanisms are necessary. Here, we reviewed the literature related to animal models of early-stage PD and pharmacological treatments capable of inducing acute dopamine impairments and/or depletion, such as reserpine, haloperidol and tetrodotoxin. We highlighted the advantages, limitations and the future prospective uses of these models, as well as their applications in the identification of novel agents for treating this neurological disorder.