Yawning behaviour has been proposed to be
associated with fatigue and recovery from stress
(Barbizet 1985, Stoessl et al. 1987). The
behaviour bas been the subject of very little
empirical research.
The activation of central cholinergic and
dopaminergic mechanisms bas been shown to induce
yawning behaviour in rats (Urba-Holmgren et al.
1977; Zarrindast and Poursoltan 1989).
Involvement of dopamine D2 receptors in yawning
behaviour bas been proposed (Yamada et al.
1986). A central cholinergic mechanism has also
been proposed to mediate the behaviour, and the
yawning induced by dopamine agonists and agents
acting on cholinoceptors is inhibited by
muscarinic antagonists, such as scopolamine and
atropine (Mogilnicka et al. 1984; Zarrindast and
Poursoltan 1989). The paraventricular nucleus
(Argiolas et al. 1987) and incerto-hypothalamic
dopamine system (Melis et al. 1987) have been
suggested to mediate yawning. Striatum is also
one of the sites involved in yawning induced by
drugs (Yamada et al. 1986).
The interaction between the GABAergic and
dopaminergic and cholinergic systems within the
striatum bas been studied (Scheel-Kruger and
Arnt 1985). GABA-mimetic drugs have been shown
to inhibit the release and turnover of striatal
acetylcholine (Stoof et al. 1979; Scatton and
Bartholini 1980, 1982), suggesting that the
activation of striatal GABAergic receptors leads
to the inhibition of striatal cholinergic
neurons. Striatal cholinergic interneurons have
been known to receive input from striatal GABA
containing cell elements (DeBoer and Westerink
1994).
Our previous work showed that
apomorphine-induced penile erection was
influenced by GABAergic receptor agonists and
antagonists (Zarrindast and Farahvash 1994).
Since the GABAergic system may interact with
cholinergic systems in brain, in the present
study, the effects of GABA-A or GABA-B receptor
agents on yawning induced by anticholinesterase
physostigmine have been evaluated.
Discussion :
The present results show that
intraperitoneal (IP) injection of the
cholinesterase inhibitor physostigmine induced
dose-dependent yawning. This is in agreement
with previous reports that activation of
cholinergic mechanism may induce yawning
(Urba-Holmgren et al. 1977, Zarrindast and
Poursoltan 1989; Zarrindast Jamshidzadeh 1992;
Zarrindast et al. 1995). In this work, the
influences of GABA-A and GABA-B receptors
activation on physostigmine-induced yawning have
been investigated. The inhibitory
neurotransmitter GABA (DeFeudis 1977; Hosli and
Hosli 1978; Johnston 1978) functions through
specific GABA receptor sites. The GABA receptors
in mammalian CNS have been divided into two
different sites, termed GABA-A and GABA-B
receptors (Bowery et al. 1980; Hill and Bowery
1981). GABA-A receptors are linked to chloride
channels (Bowery 1982), while activation of
GABA-B receptors reduces calcium currents
(Desarmenien et al. 1984; Dunlop 1984).
Present data show that either the GABA-A
receptor agonist muscimol (Bowery et al.
1984) or the GABA-B receptor agonist
baclofen (Bowery et al. 1983, 1984)
reduces yawning behaviour. Combination of
both agonists produced an even stronger
inhibitory effect. The response is a synergistic
one. These results indicate that GABAergic
system(s) may elicit a negative effect on
physostigmine-induced yawning. The competitive
GABA-A receptor antagonist bicuculline or the
non-competitive GABA-A receptor antagonist
picrotoxin (Ticku and Masky 1983) but not the
GABAB receptor antagonist phaclofen (Kerr et al.
1987) decreased the inhibitory response of
muscimol. In contrast, the response of baclofen
was reduced by the GABA-B antagonist phaclofen
but not by the GABAA antagonists. The data
indicate that both GABA-A and GABA-B receptor
stimulation may reduce cholinergic-induced
yawning separately. Similarly, our previous work
(Zarrindast and Farahvash 1994) showed that
GABA-A or GABA-B receptor activation inhibited
apomorphine-induced penile erection. The
interaction between cholinergic and GABAergic
neurons in the striatum, one of the possible
sites for yawning, has been proposed (Stoof et
al. 1979; Scatton and Bartholini 1980, 1982).
Therefore, the existing data may support an
interaction of the GABAergic and cholinergic
systems for induction of yawning.
Administration of the GABA-A or GABA-B
receptor antagonists can also reduce the yawning
induced by physostigmine. The GABA-A antagonists
bicuculline and picrotoxin may release GABA
(Mitchell and Martin 1978). Since the
antagonists can only block the pre-and
postsynaptic GABA-A, but not the GABA-B
receptors, stimulation of the postsynaptic
GABA-B sites by released GABA may inhibit
physostigmine-induced yawning.
The GABA-B autoreceptor has been shown to
regulate the release of GABA (Bonanno et al.
1989). It may be possible that blockade of
presynaptic GABAB receptors by phaclofen
releases endogenous GABA and in turn, inhibits
physostigmine-induced yawning through
stimulation of GABA-A receptors.
Considering the inhibition of the release
and turnover of the acetylcholine by GABA (Stoof
et al. 1979; Scatton and Bartholini 1980, 1982),
one may also speculate that the release of GABA
by phaclofen decreases acetylcholine levels and
inhibits physostigmine-induced yawning. The
release of GABA by either the GABA-A receptor
(bicuculline or picrotoxin) or the GABA-B
receptor antagonist (phaclofen) may decrease
yawning, while the combination of both
antagonists may block both postsynaptic GABA-A
and GABA-B receptors and thus abolish the
response of both GABA antagonists.
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
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MR, Poursoltan M Interactions of drugs
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