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11 novembre 2002
Pharmacol BiochemBehav 1989; 34; 2; 237-40
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GABAergic modulation of yawning behavior
Doger E, Urba-Holmgren R, Eguibar JR, Holmgren B
Departemento de ciencas fisiologicas , Universidad Autonoma de Puebla, Mexico
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren


Yawning is a discrete innate motor pattern widely represented in the behavioral repertoire among vertebrates. It occurs spontaneously at variable frequencies, and is subject to a complex set of neurotransmitter and hormonal influences. Yawning can be induced by cholinomimetic drugs such as physostigmine and pilocarpine, and is inhibited by scopolamine. It may also be evoked by low doses of apomorphine (APO), and other dopamine (DA) receptor agonists (- 3PPP and bromocriptine). With higher doses of APO, which also act upon postsynaptic receptors, spontaneous and physostigmine-induced yawning are inhibited. In spite of the fact that other substances, like the peptide hormones ACTH, alpha-MSH, prolactin and oxytocin, are yawning inducers, several authors agree in assigning a crucial role in the regulation of yawning to the DA-acetylcholine (ACh) interaction.

Links between ACh and DA neurons have been properly described in the septo-hippocampal pathway and the striatum. It has been described that stimulation and lesion of these structures affect yawning frequency.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the principal efferent systems related to the nigro-striatal and the ventral tegmental-nucleus accumbens dopaminergic systems. Also, it is well known that GABAergic neurons regulate dopaminergic and cholinergic activities in these structures. Therefore, it seemed important to explore the role of the GABA system in the regulation of yawning behavior. Two different types of GABA receptors have been described, GABAA and GABAB. The former are sensitive to muscimol and THIP, and are antagonized by bicuculline. Receptors of this kind are mostly situated postsynaptically, and are coupled to chloride channels. The other type of GABA receptors, GABAB, are not sensitive to bicuculline, their most specific agonist is baclofen; they are mostly presynaptic and are involved in the modulation of ACh release.

The experiments here reported have been performed with GABAmimetic drugs and GABA antagonists. The use of two sublines of rats with high and low spontaneous yawning frequency has allowed us to study the effect of these GABA-active drugs, both on spontaneous and drug-induced yawning.

Discussion : In order to evaluate the possible role of the GABA system in the regulation of yawning we studied the effects of different GABA-active drugs upon this behavior.

The decrease in spontaneous yawning frequency observed with baclofen (GABAB agonist) suggests that GABA neurons play a role in yawning regulation. This decrease may be caused by a lower central cholinergic tone, due to a presynaptic GABAergic modulatory action on cholinergic terminals. This sort of modulation has been described in both peripheral and central nervous systems.

Seeking further evidence to support the idea that baclofen acts by modulating ACh release, we tested its effect upon physostigmine-induced yawning. Since physostigmine effects, as an indirect cholinergic agonist, depend on ACh being released, we should expect that baclofen would decrease physostigmine-induced yawning frequency. Our results agree with this assumption.

Administration of THIP (GABAA agonist) does not change yawning frequency. At a first glance, this might mean that only GABAB receptors participate in the regulation of this behavior. Nevertheless, the increase of spontaneous and physostigmine induced yawning obtained with GAG, suggests that GABA may also inhibit an inhibitory pathway acting upon yawning trigger neurons. The reduced yawning frequency observed with bicuculline (GABAA antagonist) also supports this statement. On the other hand, the GAG dose response curve with only one effective dose-might be understood as due to GABA effects on two sets of GABA receptors with different sensitivities and opposite actions on yawning behavior.

Summarizing, our results suggest that GABA neurons play a role in yawning regulation at two sites:

  1. controlling ACh release at cholinergic terminals, through GABAB receptors
  2. modulating the activity of dopaminergic yawning-inhibitory influences through GABAA receptors.


  • Melis MR , A.Argiolas. Reduction of drug-induced yawning and penile erection and of noncontact erections in male rats by the activation of GABAA receptors in the paraventricular nucleus: involvement of nitric oxide Eur J Neurosci 15(5): 852-60.(2002)
  • Melis MR, Spano MS, Succu S, Argiolas A Activation of gamma-aminobutyric acid(A) receptors in the paraventricular nucleus of the hypothalamus reduces apomorphine-, N-methyl-D-aspartic acid- and oxytocin-induced penile erection and yawning in male rats. Neurosci Lett 2000 Mar 10;281(2-3):127-30
  • Zarrindast MR, Toloui V, Hashemi B Effects of GABAergic drugs on physostigmine-induced yawning in rats; Psychopharmacology (Berl) 1995 Dec;122(3):297-300
  • Paredes RG, Karam P, Highland L, Agmo A GABAergic drugs and socio-sexual behavior Pharmacol BiochemBehav 1997; 58(2):291-298