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

mise à jour du 6 février 2003
PharmacolBiochem Behav 1988;29(1):59-62

Prolactin-induced yawning behavior requires an intact nigro-striatal dopamine system
Laping NJ, Ramirez VD
Department of Physiology and Biophysics, University of Illinois, Urbana, Illinois


-Laping NJ, Ramirez VD Prolactin-induced yawning behavior requires an intact nigro-striatal dopamine system Pharmacol Biochem Behav 1988;29(1):59-62
-Laping NJ, Ramirez VD Prolactin induces yawning and the stretching yawning syndrome in young adulte male rats. Hormones & Behavior 1986;20:49-59
-Laping NJ, Ramirez VD.Yawning behavior in male rats is associated with decreases in in vivo DOPAC efflux from the caudate nucleus. Behav Brain Res. 1990;36(1-2):65-72.
Prolactin, a protein hormone of pituitary origin, induces an array of behaviors in a variety of animals. In rats, maternal, feeding and grooming behaviors, as weil as learning and memory processes, have been reported to be influenced by prolactin (PRL). Presumably these behavioral effects represent a CNS site of action. A neurotransmitter known to be involved in the mediation of some of the effect of PRL on the CNS is dopamine. It is known that PRL in rats stimulates the tuberoinfundibular dopamine system and the nigrostriatal dopamine system. One behavior that appears to be affected by PRL and dopamine (DA) is yawning. For example, apomorphine (APO) at low doses is able to evoke yawning, while at higher doses it is ineffective.
Moreover, preliminary observations within our own laboratory indicate that PRL infused locally into a restricted area of the caudate nucleus could also induce yawning behavior in male rats. Also APO-induced yawning in male rats is markedly suppressed following hypophysectomy providing additional evidence linking PRL and DA to yawning or after castration. In this latter condition yawning behavior can be restored with testosterone ) or with dihydro testosterone. It is then possible that in addition to testicular hormones, pituitary hormones are somehow involved in APOinduced yawning in male rats. In addition it is known that pituitary output and DA levels change over a circadian cycle. Also there is now evidence that the number of spontaneous yawns varies with the time of day. Therefore in the present experiments we have explored the systemic action of PRL on this discrete behavior of relatively low spontaneous frequency which can be easily quantified and studied. Thus we address two questions:
  1. Can different doses of systemic PRL induce yawning in male rats?
  2. Is the responsivity to PRL-evoked yawning dependent on the time of day?
Discussion :

We have shown that oPRL injected subcutaneously in the neck induces yawning and/or SYS in young adult male rats. A bell-shaped dosedependant response characterized this phenomenon with 0.25 lig/kg being the most effective dose. In addition, the number of yawns varies with the time of day. Both APO and oPRL induced a significantly greater yawning frequency at 1600 than at 1000 hr. Even though both compounds induced an identical behavior the latency of yawning was different. APO, at low doses, at which it is thought to stimulate autoreceptors, had a short latency, 12 min at 1000 hr, whereas PRL which increases DA release, had a longer latency, 37 min at 1000 hr.

APO has been known to induce other stereotyped behaviors. At high doses, greater than 250 µg/kg, APO induces continuous licking, sniffing, and chewing which is sometimes accompanied by constant movement, and at this dose APO is thought to stimulate DA postsynaptic receptors. However, lower doses of APO (50-100 gg/kg) induce yawning behavior and it is thought that APO at these doses is acting on the presynaptic autoreceptors, inhibiting DA release, and causing an increase in the firing of the cholinergic neurons in the corpus striatum which are under inhibitory control by the nigro striatal dopamine system. Furthermore there is evidence that cholinomimetic drugs are effective in evoking yawning. Thus the conclusion is that the DA system inhibits the -yawning generator- via inhibiting cholinergic neurons.

However, there are other factors involved in yawning. Protein hormones such as adrenocorticotrophic hormone (ACTH), melanocyte-stimulating hormone (MSH), and lipotrophic hormone when injected intracerebrally induce yawning in a variety of mammals. Also when rats are hypophysectomized the ability to yawn in response to APO is lost. Presumably one or more hormones of the pituitary are involved in yawning behavior. ACTH and MSH have been shown to be important and now we have demonstrated prolactin's effectiveness in physiological doses. But if APO induces yawning by acting on the DA autoreceptors and inhibiting DA transmission, how does PRL induce yawning if it is said to facilitate DA transmission ?

After initial stimulation PRL could cause a secondary inhibition of the nigrostriatal dopamine system.Groves showed that infusing the caudate putamen with amphetamine (which facilitates DA transmission) resulted in a decrease of the firing rate of the substantia nigra after a time lag of approximately 30 min. This latency follows our own finding that PRL will induce yawning behavior after a mean laiency of 37 min. There is evidence of DA stores in the dendrites of the dopaminergic neurons of the substantia nigra. Furthermore, it bas been shown that if DA is applied to the dendrites of these neurons they will then decrease their firing rate. Thus there are at least two possible ways in which PRL may cause eventual inhibition of the DA system. First, after PRL releases dopamine, this neurotransmitter then binds to its presynaptic autoreceptors and inhibits further DA release. Secondly, PRL may release dopamine stored in the dendrites of the dopaminergic cell bodies in the substantia nigra which will bind to dendritic autoreceptors and cause a decrease in the firing rate of the DA neurons. This decrease of doparninergic activity results in lifting of the inhibitory control on the cholinergic neurons which then will activate the yawning behavior.

Since yawning behavior is influenced by pituitary hormones it is reasonable to consider that the cyclicity of pituitary hormone output may change the responsivity of the -yawning center.- Indeed, if we compare circadian levels of PRL and ACTH with the spontaneous and PRL-induced yawning during a circadian cycle one finds that PRL and ACTH levels are high in the late afternoon and night when the spontaneous and PRL-induced yawning frequencies are also high. Thus PRL and perhaps other pituitary hormones by themselves or in a synergistic fashion increase the sensitivity or responsivity of the -yawning generator.- The physiological relevance of PRL as well as other peptides affects on yawning behavior remain to be elucidated.

-Sato F et al. Suppressive effects of chronic hyperprolactinemia on penile erection and yawning following administration of apomorphine to pituitary-transplanted rats Journal of Anthology 1997; 18; 1; 21-25