Article

Cellular and Molecular Neurobiology

, Volume 25, Issue 2, pp 371-392

Role of Nitric Oxide on Motor Behavior

  • E. A. Del BelAffiliated withDepartment MEF Physiology, School of Odontology, Medical SchoolDepartmentMEF-Physiology, School of Odontology Email author 
  • , F. S. GuimarãesAffiliated withDepartment of Pharmacology, Medical School
  • , M. Bermũdez-EcheverryAffiliated withDepartment MEF Physiology, School of Odontology, Medical School
  • , M. Z. GomesAffiliated withDepartment MEF Physiology, School of Odontology, Medical SchoolDepartment of Physiology, Medical School
  • , A. Schiaveto-de-SouzaAffiliated withDepartment MEF Physiology, School of Odontology, Medical School
  • , F. E. Padovan-NetoAffiliated withDepartment MEF Physiology, School of Odontology, Medical School
  • , V. TumasAffiliated withDepartment MEF Physiology, School of Odontology, Medical School
  • , A. P. Barion-CavalcantiAffiliated withDepartment MEF Physiology, School of Odontology, Medical SchoolDepartment of Neurology, Medical School
  • , M. LazzariniAffiliated withDepartment MEF Physiology, School of Odontology, Medical SchoolDepartment of Neurology, Medical School
    • , L. P. Nucci-da-SilvaAffiliated withDepartment MEF Physiology, School of Odontology, Medical School
    • , D. de Paula-Souza1Affiliated withDepartment MEF Physiology, School of Odontology, Medical School

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Abstract

The present review paper describes results indicating the influence of nitric oxide (NO) on motor control. Our last studies showed that systemic injections of low doses of inhibitors of NO synthase (NOS), the enzyme responsible for NO formation, induce anxiolytic effects in the elevated plus maze whereas higher doses decrease maze exploration. Also, NOS inhibitors decrease locomotion and rearing in an open field arena.

These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), N G -nitro-L-arginine methylester (L-NAME), N G -monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration.

Acute administration of L-NOARG has an additive cataleptic effect with haloperidol, a dopamine D2 antagonist. The catalepsy is also potentiated by WAY 100135 (5-HT1a receptor antagonist), ketanserin (5HT2a and alfa1 adrenergic receptor antagonist), and ritanserin (5-HT2a and 5HT2c receptor antagonist). Atropine sulfate and biperiden, antimuscarinic drugs, block L-NOARG-induced catalepsy in mice.

L-NOARG subchronic administration in mice induces rapid tolerance (3 days) to its cataleptic effects. It also produces cross-tolerance to haloperidol-induced catalepsy. After subchronic L-NOARG treatment there is an increase in the density NADPH-d positive neurons in the dorsal part of nucleus caudate-putamen, nucleus accumbens, and tegmental pedunculupontinus nucleus. In contrast, this treatment decreases NADPH-d neuronal number in the substantia nigra compacta.

Considering these results we suggest that (i) NO may modulate motor behavior, probably by interfering with dopaminergic, serotonergic, and cholinergic neurotransmission in the striatum; (ii) Subchronic NO synthesis inhibition induces plastic changes in NO-producing neurons in brain areas related to motor control and causes cross-tolerance to the cataleptic effect of haloperidol, raising the possibility that such treatments could decrease motor side effects associated with antipsychotic medications.

Finally, recent studies using experimental Parkinson’s disease models suggest an interaction between NO system and neurodegenerative processes in the nigrostriatal pathway. It provides evidence of a protective role of NO. Together, our results indicate that NO may be a key participant on physiological and pathophysiological processes in the nigrostriatal system.

Keywords

catalepsy L-NOARG 7-NIO nitric oxide synthase L-arginine haloperidol tolerance dopamine NADPH-diaphorase intracerebral injection anxiogenic anxiolytic Parkinson