title: The preferential nNOS inhibitor 7-nitroindazole and the non-selective one N(G)-nitro-L-arginine methyl ester administered alone or jointly with L-DOPA differentially affect motor behavior and monoamine metabolism in sham-operated and 6-OHDA-lesioned rats.
abstract: 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 (50mg/kg) induced a distinct catalepsy 30 min after injection but only 7-NI impaired spontaneous locomotion after 10 min. In 6-OHDA-lesioned rats, chronic L-DOPA (25mg/kg) induced 2.5-h long contralateral rotations. 7-NI (30 and 50mg/kg) markedly reduced the intensity of L-DOPA-induced contralateral rotations while extending their duration until 4.5h whereas L-NAME (50 and 100mg/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.
authors: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors: Anna
authors: A
authors: Czarnecka
authors: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors: Jolanta
authors: J
authors: Konieczny
authors: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors: Tomasz
authors: T
authors: Lenda
authors: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland. Electronic address: lorenc@if-pan.krakow.pl.
authors: Elżbieta
authors: E
authors: Lorenc-Koci
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007191:Indazoles / Q000627:therapeutic use*; D007980:Levodopa / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D007191:Indazoles; D018696:Neuroprotective Agents; D007980:Levodopa; D016627:Oxidopamine; D001058:Apomorphine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester
keywords: 7-nitroindazole; Dopamine metabolism; L-NAME; Motor behavior; Nitric oxide; l-DOPA