L-DOPA modulation of corpus striatal dopamine and dihydroxyphenylacetic acid output from intact and 6-OHDA lesioned rats

Abstract

In the present report we examined the differences in in vitro dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) efflux from the corpus striatum (CS) of intact versus 6-hydroxydopamine (6-OHDA) lesioned (in substantia nigra) male rats in response to different doses of two pulse infusions of L-dihydroxyphenylalanine (L-DOPA). In the first experiment, we tested the effects of two 20-min infusions of 5 uM L-DOPA. In the second experiment we repeated this protocol using 50 uM L-DOPA. There was an overall significantly greater output of DA for intact versus 6-OHDA lesioned rats for both doses. Moreover, in Experiment 1, the 5 uM L-DOPA produced a peak DA response to the second infusion which was significantly higher than that of the first infusion in the intact, but not lesioned rats. In Experiment 2, the 50 uM L-DOPA group showed no significant differences in DA output between the two infusions for both intact and lesioned rats. In contrast to DA responses, there were no overall significant differences in DOPAC output between intact and 6-OHDA lesioned rats for both doses. However, for both doses tested, the peak DOPAC output from the second infusion was significantly increased in lesioned, but not intact rats. These data demonstrate that L-DOPA evoked DA and DOPAC output are differentially modulated in intact and 6-OHDA lesioned striatum. The lesions of the striatal dopaminergic system may alter these responses through changes in intraneuronal storage and metabolism of DA following L-DOPA infusion.

Cortical Stimulation Evokes Abnormal Responses in the Dopamine-Depleted Rat Basal Ganglia

“…Thus, activation of these D2-Rs by DA converted from L-DOPA in Str may underlie the observed effects (Xu and Dluzen, 1996; Tanaka et al, 1999). However, intra-Str methyl-L-DOPA had a minor effect on the restoration of the short inhibition in GPi.…”

Role of Striatum in the Pause and Burst Generation in the Globus Pallidus of 6-OHDA-Treated Rats

“…DA-depletion increases D2-R expression in Str–GPe neurons (Gerfen et al, 1990) and also sensitizes D2-Rs on cortico-Str terminals (Bamford et al, 2004). Thus, the changes may be due to activation of these D2-Rs by DA converted from l -DOPA in Str (Xu and Dluzen, 1996; Tanaka et al, 1999). The elucidation of the l -DOPA effects on spontaneous firing and the cortical and thalamic stimulation-induced responses of Str neurons will be the subjects of future investigations.…”