Dopamine agonist-induced yawning in rats: a dopamine D3 receptor mediated behavior
Collins G et al

mise à jour du
23 septembre 2004
2004; 71; 169-173

Nitric oxide agents and
apomorphine induced rat behaviors
M. Zarrindast, K Nojoomi, et al
Department pharmacology, Teheran University of medical sciences


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.
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.