Electrophysiological and neurochemical characterization of 7-nitroindazole and molsidomine acute and sub-chronic administration effects in the dopaminergic nigrostrial system in rats.
Nitric oxide (NO) plays an important role in the integration of information processed by the basal ganglia nuclei. Accordingly, considerable evidence has emerged indicating a role for NO in pathophysiological conditions such as Parkinson's disease (PD) and other neurodegenerative disorders. Despite these recent advances, the nitrergic modulation of the dopamine (DA) nigrostriatal system is still unclear. In order to fill this gap, in this study we used in vivo electrophysiology and ex vivo neurochemical analysis to further investigate the effect of NO signaling in rat substantia nigra pars compacta (SNc) and the striatum. Acute and subchronic (4 days) pharmacological manipulation of the NO system using 7-nitroindazole (7-NI, 50 mg kg(-1) i.p.) and molsidomine (MOL, 40 mg kg(-1) i.p.) treatment caused significant changes in both DA SNc neurons electrophysiological properties and striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. It is worth noting that acute inhibition of NO production decreased DA nigrostriatal neurotransmission while its subchronic inhibition was instead excitatory. Thus, a crucial role for NO in the modulation of nigrostriatal DA function is suggested together with a potential role for inhibitors of NO sythase in the treatment of PD.
Di Matteo
Vincenzo
V
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, S. Maria Imbaro (CH), Italy.
Pierucci
Massimo
M
Benigno
Arcangelo
A
Orbán
Gergely
G
Crescimanno
Giuseppe
G
Esposito
Ennio
E
Di Giovanni
Giuseppe
G
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007191:Indazoles / Q000008:administration & dosage*; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D007191:Indazoles; D020030:Nitric Oxide Donors; D015102:3,4-Dihydroxyphenylacetic Acid; D008981:Molsidomine; C080122:7-nitroindazole; D004298:Dopamine