Age-Related Neostriatal Alterations in the Rat: Failure of L-DOPA to Alter Behavior

Abstract

Age differences in rotational behavior were examined in young (6 mo) and old (24 mo) Wistar rats lesioned in the left substantia nigra with 6-OHDA. Young animals showed a 50% increase in rotational behavior with L-DOPA pretreatment and a 15–20% increase following L-tyrosine pretreatment. However, neither L-DOPA nor L-tyrosine pretreatment potentiated amphetamine-induced rotational behavior of senescent animals. Pretreatment with tranylcypromine, an MAO inhibitor, did not enhance rotational behavior in either group. After assessing rotational responses to amphetamine, half of each age group was given L-DOPA 1 hr prior to sacrifice, and right (RS) and left striatal (LS) levels of dopamine (DA) were examined in all groups. Comparable LS depletion was found in both age groups. L-DOPA significantly raised DA levels in the RS of the young animals while causing no change effect in old animals although the amount of L-DOPA entering the striatum was even higher in the senescent animals. Striatal tyrosine hydroxylase showed only a small decrease (15%) in activity, while DOPA decarboxylase activity showed no significant age-related decline. Despite the lack of substantial decrease in enzyme activity, the results indicate an age-dependent decrease in the capacity for L-DOPA potentiation of rotational behavior. Defects may exist at the level of elevation of the functional pool of DA, the release of DA, or the interaction of DA with a decreasing number of a class of DA receptors involved in motor control.