Enhanced effects of 6-hydroxydopamine on evoked overflow of striatal dopamine in aged rats

Abstract

Nigrostriatal dopamine neurons degenerate during aging, and the excessive loss of dopamine neurons that occurs with Parkinson’s disease is usually confined to older individuals. Although 6-hydroxydopamine lesioning of the nigrostriatal dopamine system is a common method for producing animal models of dopamine neuron degeneration, there have been relatively few studies that have examined the effects of 6-hydroxydopamine on the dopamine systems of aged animals. The present experiments were designed to determine if nigrostriatal dopamine neurons in aged rats are more sensitive to the neurotoxic effects of 6-hydroxydopamine than those of younger rats. Young (4-month-old), middle-aged (14-month-old) and aged (24-month-old) Fischer-344 rats were given a single injection of vehicle, 50 or 100 μg 6-hydroxydopamine into the right lateral ventricle. Three to four weeks later in vivo electrochemistry was used to measure potassium-evoked overflow of dopamine in the striatum. In the young rats the 50-μg dose had no significant effect on evoked overflow of dopamine in the striatum or on post-mortem levels of dopamine in the striatum or substantia nigra. The higher dose in the young animals diminished evoked overflow of dopamine as well as tissue levels of dopamine. In the aged rats both doses of 6-hydroxydopamine led to significant decreases in evoked overflow of striatal dopamine and in tissue levels of dopamine in the striatum and substantia nigra. These results suggest that dopamine neurons of aged Fischer-344 rats are more susceptible to the toxic effects of 6-hydroxydopamine than those of younger animals.