Effects of Subchronic Treatment With Selegiline on L-DOPA-Induced Increase in Extracellular Dopamine Level in Rat Striatum

Abstract

Abstract. Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine (DA) level in awake rats treated with L-DOPA and/ or selegiline using a microdialysis method. Rats given 10 mg / kg, i.p. per day selegiline for 7 days were administered with a single dose of 100 mg / kg, i.p. L-DOPA 0 (3 h), 1, 3, 7, 14, 21, or 28 days after the last selegiline treatment. Carbidopa was administered 0.5 h before L-DOPA administration. The significant increase in basal DA level before L-DOPA treatment persisted until 1 day after the last selegiline treatment, and the significant decrease in basal DOPAC level persisted for more than 28 days. Thus, selegiline affected DA catabolism for more than 28 days. Total monoamine oxidase (MAO) and MAO-B activities at day 0 decreased by 22% and 5.7%, respectively. The significant enhancement of L-DOPA-induced increase in DA level was observed until 3 days after the last selegiline treatment. Next, the effects of reducing L-DOPA dose by 25% were examined 3 h after the last selegiline treatment. A dose-dependent decrease in DA level was observed, indicating that DA level in selegiline-treated rats can be controlled by L-DOPA dose.

Selective inhibition of monoamine oxidase A or B reduces striatal oxidative stress in rats with partial depletion of the nigro-striatal dopaminergic pathway

“…These results are in agreement with findings of ourselves and other studies showing that MAO-A is the major enzyme responsible for DA oxidative breakdown in both normal and 6-OHDA-lesioned striatum (Finberg et al, 1995;Lamensdorf et al, 1996;Wachtel and Abercrombie, 1994). It should be noted, however, that Adachi (Adachi et al, 2006) observed a reduction in [DA ec ] levels following L-dopa treatment in rats treated subchronically with selegiline, and attributed this effect to presynaptic inhibitory activation.…”

Reuptake of L‐DOPA‐derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter

“…Clearance of neurotransmitters from the extracellular space is executed by reuptake, enzymatic degradation, and dilution by diffusion (Garris and Wightman, 1995). Adachi et al (2006) demonstrated that a monoamine oxidase B inhibitor increased levels of L-DOPAderived DA in the DA-denervated striatum, indicating the involvement of the enzymatic degradation. A recent study suggests that diffusion mechanisms in the clearance of monoamines should not be ignored (Cragg et al, 2001).…”