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:
controlling ACh release at cholinergic
terminals, through GABAB receptors
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
