Reciprocal interactions between nitrergic and dopaminergic systems play a key role in the control of motor behavior. In the present study, we performed a comparative analysis of motor behavior (locomotor activity, catalepsy, rotational behavior) and monoamine metabolism in the striatum and substantia nigra of unilaterally sham-operated and 6-OHDA-lesioned rats treated with the preferential neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) or the non-selective one N-G-nitro-L-arginine methyl ester (L-NAME), alone or in combination with L-DOPA. Each NOS inhibitor given alone (50 mg/kg) induced a distinct catalepsy 30 min after injection but only 7-NI impaired spontaneous locomotion after 10 mm. In 6-OHDA-lesioned rats, chronic L-DOPA (25 mg/kg) induced 2.5-h long contralateral rotations. 7-NI (30 and 50 mg/kg) markedly reduced the intensity of L-DOPA-induced contralateral rotations while extending their duration until 4.5 h whereas L-NAME (50 and 100 mg/kg) only tended to attenuate their intensity without affecting the duration. 7-NI but not L-NAME significantly increased endogenous tissue DA levels in the nigrostriatal system of both sham-operated and 6-OHDA-lesioned rats. In L-DOPA-treated group, 7-NI significantly enhanced the L-DOPA-derived tissue DA content in this system and decreased the level of the intracellular DA metabolite DOPAC produced by monoamine oxidase (MAO). In contrast to 7-NI, L-NAME decreased markedly DA content and did not affect DOPAC level in the ipsilateral striatum. It means that the differences in 7-NI and L-NAME-mediated modulation of L-DOPA-induced behavioral and biochemical effects resulted not only from the inhibition of NOS activity but also from differences in their ability to inhibit MAO. (C) 2015 Elsevier B.V. All rights reserved.
