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Electrophysiological and Neurochemical Characterization of 7-Nitroindazole and Molsidomine Acute and Sub-Chronic Administration Effects in the Dopaminergic Nigrostrial System in Rats

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Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 73))

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Abstract

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.

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Abbreviations

6-OHDA:

6-hydroxydopamine

7-NI:

7-nitroindazole

ACh:

Acetylcholine

BBB:

Blood brain barrier

DA:

Dopamine

DOPAC:

3,4-dihydroxyphenylacetic acid

l-ARG:

l-Arginine

l-NAME:

N-ω-nitro-l-arginine methyl ester

l-NOARG:

l-nitro-arginine

MAO:

Monoamine oxidase

MOL:

Molsidomine

NNLA:

N-nitro-l-arginine

nNOS:

Neuronal NO synthase

NO:

Nitric oxide

oPFC:

Orbital prefrontal cortex

PD:

Parkinson’s disease

POPAC:

Dihydroxyphenilacetic acid

PPT:

Pedunculopontine tegmental nucleus

SIN-1:

3-morpholinosydnonomine

SNc:

Substantia nigra pars compacta

VTA:

Ventral tegmental area

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Acknowledgments

This study was supported in part by Ateneo di Palermo research funding, project ORPA068JJ5, coordinator G. D.; G. O. was supported by an Italian Ministry of the University and Scientific Research fellowship (Tutor: G. D.).

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Authors and Affiliations

  1. Istituto di Ricerche Farmacologiche “Mario Negri”, Consorzio Mario Negri Sud, S. Maria Imbaro, CH, Italy

    Vincenzo Di Matteo, Massimo Pierucci & Ennio Esposito

  2. Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana “G. Pagano”, Università degli Studi di Palermo, Corso Tuköry 129, 90134, Palermo, Italy

    Arcangelo Benigno, Gergely Orbán, Giuseppe Crescimanno & Giuseppe Di Giovanni

Authors
  1. Vincenzo Di Matteo
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  2. Massimo Pierucci
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  3. Arcangelo Benigno
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  4. Gergely Orbán
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  5. Giuseppe Crescimanno
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  6. Ennio Esposito
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  7. Giuseppe Di Giovanni
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Correspondence to Giuseppe Di Giovanni .

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Editors and Affiliations

  1. Fac. Medicina e Chirurgia, Università di Palermo, Corso Tukory 129, Palermo, 90134, Italy

    Giuseppe Giovanni

  2. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Vincenzo Di Matteo

  3. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Ennio Esposito

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Di Matteo, V. et al. (2009). Electrophysiological and Neurochemical Characterization of 7-Nitroindazole and Molsidomine Acute and Sub-Chronic Administration Effects in the Dopaminergic Nigrostrial System in Rats. In: Giovanni, G., Di Matteo, V., Esposito, E. (eds) Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra. Journal of Neural Transmission. Supplementa, vol 73. Springer, Vienna. https://doi.org/10.1007/978-3-211-92660-4_14

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  • DOI: https://doi.org/10.1007/978-3-211-92660-4_14

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