The effect of the non-selective nitric oxide synthase inhibitor L-name on rotational behaviour and dopamine metabolism in 6-OHDA-lesioned rats treated chronically with L-DOPA

Abstract

The strong evidence obtained from in vivo and ex-vivo studies suggests an interaction between the dopaminergic and nitrergic systems. The aim of this study was to assess whether the inhibition of nitric oxide synthesis in 6-OHDA-lesioned rats treated chronically with L-DOPA affects rotational behaviour and dopamine (DA) metabolism. Male Wistar rats were injected unilaterally with a single dose of 6-OHDA (8 μg/4 μl) into the left medial forebrain bundle. After two weeks, only rats exhibiting a substantial loss of nigrostriatal neurons were treated chronically with L-DOPA (25 mg/kg) once daily for 15 days. On day 14, the rats received single doses of L-NAME (50 or 100 mg/kg) ten minutes before L-DOPA injection, and rotational behaviour was recorded for more than 2 h. On the following day, 1 h after the last injections of L-NAME and L-DOPA, animals were killed. The levels of dopamine (DA) and its metabolites (DOPAC, HVA) were assayed in striatal and nigral homogenates using an HPLC method. A single dose of L-NAME (50 mg/kg), administered before the penultimate dose of L-DOPA, caused contralateral rotations whose intensity was lower than that produced by L-DOPA alone. Moreover, such a combined treatment decreased striatal and nigral DA, DOPAC and HVA levels on the lesioned side compared to administration of L-DOPA alone. On the contralateral side, decreases in the content of DA metabolites only were observed. The higher dose of L-NAME produced weaker effects. Our biochemical results suggest that L-NAME prevents DA formation from L-DOPA, which eventually leads to attenuation of the L-DOPA-induced rotations.