- Introduction
- Nitric oxide (NO), a radical gas molecule
and a conventionally known vasodilator, has been
recognized as an
- intracellular and intercellular messenger
molecule in the central nervous system. NO is
synthesized from L-arginine
- by the heme protein NO synthase (NOS). It
has been shown that inhibition of the NO pathway
can prevent some biochemical and behavioral
changes evoked by psychostimulants. It has been
reported that NO can affect the central dopamine
system, mainly the nigrostriatal system, but
with conflicting results.
-
- Studies using in vivo microdialysis or
voltammetry showed that NO may stimulate or
inhibit dopamine release in the striatum. It
evokes the release of [3H]-dopamine from
rat striatal tissue and cultured fetal
dopaminergic neurons, and inhibits the dopamine
reuptake carrier.
-
- Furthermore, it has been shown that NO
stimulates in vivo dopamine release by a cyclic
GMP-dependent route and can inhibit it through
formation of peroxynitrite. It has been proposed
that dopamine D2-receptor activation may
suppress NOS activity. In order to determine
whether the NO pathway also participates in the
stereotypic effect of dopamine, we evaluated the
effects of the NOS inhibitor,
NG-nitro-L-arginine methyl ester (L-NAME), and
the NO precursor,
2-(S)-2-amino-5-[(aminoiminomethyl)
amino] pentatonic acid (L-arginine), on
apomorphine-induced behavior.
-
- Discussion
- The present results clearly demonstrate that
the NOS precursor, L-arginine, and the NOS
inhibitor, L-NAME, altered behavior induced by
the D1/D2-dopamine receptor agonist,
apomorphine. L-Arginine decreased licking
induced by apomorphine. There is evidence
that D1- and D2-dopamine receptors regulate NO
release. NO has also been shown to regulate
adenylate cyclase activity i rat striatal
membranes and attenuates
neuromodulatorstimulated cAMP signaling in the
striatum. Since both D1- and D2-dopamine
receptors are involved in licking behavior and
D1- and D2-dopamine receptors increase or
decrease cAMP levels, respectively, the
involvement of cAMP in the decrease of
apomorphine-
- induced licking by L-arginine seems
unlikely.
-
- The NOS inhibitor, L-NAME, also decreased
apomorphine induced licking. Thus it seems
possible that apomorphine induces its response
through NO production. The effect of L-NAME,
however, may be supported by data indicating
that inhibition of the NO pathway can prevent
some biochemical and behavioral changes evoked
by psychostimulants.
-
- NO induces release of neurotransmitters by
Ca2+- dependent and independent mechanisms,
including acetylcholine,
- dopamine, norepinephrine, GABA, excitatory
amino acids, etc. NO may also facilitate
NMDAinduced burst firing in dopaminergic
neurons. Therefore, these opposite responses can
be explained by the involvement of these
neurotransmitters. It has been shown that
L-arginine biphasically influences dopamine
release. A low concentration of L-arginine
transiently reduced the release of dopamine,
which is reversed to sustained increased outflow
when high concentrations are applied. On the
other hand, the other reports indicate that
L-arginine-induced changes in the dopamine
outflow seem to be NO independent because they
are not influenced by 7-nitroindazole a
selective neuronal NOS inhibitor. Thus one can
propose that NO may exert a modulatory influence
on the mechanism of dopaminergic- induced
licking.
-
- Yawning is a stereotyped behavior
which can occur alone or in combination with
stretching and/or penile erection in humans and
animals. It seems that acetylcholine, dopamine,
oxytocin, excitatory amino acids, serotonin,
etc. are involved in the behavior. The present
data show that apomorphine induced yawning and
penile erection, which is supported by our
previous results. Some
results provide support for a neurotransmitter
role of central NO in the control and expression
of yawning and penile erection. Both
yawning and penile erection are induced through
D2- dopamine receptor activation, while D1
inhibits the behavior. Furthermore, dopamine may
decrease or increase NOS through D1- and
D2-dopamine receptors, respectively. It has been
shown that NOS inhibitors increase cAMP levels
in all areas of CNS. Cyclic AMP has also been
proposed to decrease yawning, and therefore,
inhibition of yawning by L-NAME may be due to
this mechanism. Moreover, L-arginine, which
increases, and L-NAME, which decreases NO
levels, decreased the apomorphine-induced
yawning. It appears that NO in some
circumstances can increase or decrease
acetylcholine, serotonin, dopamine,
noradrenaline. So these controversial responses
can be explained by the dual effect of the
agent.
-
- In the present study, in agreement with
others , apomorphine induced penile erection.
However, its response was not altered by
L-arginine. While apomorphine-induced penile
erection may be mediated centrally, the response
of NO seems to be due to a peripheral mechanism
. Our data indicate that L-NAME (10 mg/kg) also
increased apomorphine-induced penile
erection.
-
- In conclusion our results show that
central NO does not play a crucial role in the
exertion of the response. It has been shown that
NO exerts a dual inhibitory and facilitatory
action on hippocampal evoked potentials. It also
produces a dual effect on neuronal
responsiveness in a highly seizure-prone brain
region. These results may support our present
data that NO elicited a dual effect on
apomorphine-induced behaviors and modulates the
effects of apomorphine-induced behaviors in rat.
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