'Non-specific' mechanisms of neuronal damage in amphetamine neurotoxicity in the rodent striatum

Abstract

The neurochemical consequences of amphetamine administration at toxic dosage are complex. The specificity of damage to dopaminergic neurons is based on the ability of amphetamine and methamphetamine to release dopamine and elicit its redistribution. The changes inside the synaptic terminals of dopaminergic neurons in the striatum due to this redistribution initiate a wide spectrum of non-specific mechanisms of neuronal damage. Excitotoxicity and metabolic and oxidative stress are involved and play critical roles in amphetamine neurotoxicity. On the other hand, amphetamine administration elicits changes in endogenous neuroprotection that are important in damage prevention. Although the fine mechanisms of cell interactions, intraneuronal changes and involvement of various neurotransmitter systems in metabolic and oxidative stress are not completely understood, the data available offer prospects of developing neuroprotective therapy.