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 alfal
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.