- Introduction Yawning behaviour has
been suggested to be a physiological response
associated with fatique and recovery from stress
(Barbizet,
1958; Stoessl
et al., 1987). Although yawning is a curious
and still little understood behaviour which is
displayed in many vertebrate species (Baenninger,
1987), it is nonetheless a discrete and
easily quantifiable behaviour that can be used
as a model for the understanding of various
central nervous system functions. Current models
based on pharmacological experiments suggest
that cholinergic and dopaminergic systems induce
yawning behaviour in rats. Interaction between
cholinergic and dopaminergic systems in yawning
behaviour (Mogilnicka
et al., 1984; Zarrindast
and Poursoltan, 1989) and also between
dopaminergic (Brown et al., 1991) or cholinergic
systems (Brown et al., 1990) with an adenosine
mechanism has been shown.
Adenosine plays a functionally important role
in nervous tissue as a regulator of neural
activity (Phillis and Wu, 1981; Snyder, 1985).
Adenosine inhibits neural firing and release of
neurotransmitters such as acetylcholine,
gamma-aminobutyric acid, dopamine,
norepinephrine and glutamate in the brain (Harms
et al., 1979; Fredholm and Hedqvist, 1980;
Stone, 1981; Dolphin and Archer, 1983; Spignoli
et al., 1984; O'Regan and Phillis, 1987).
Adenosine receptors have been divided into A1
and A2 subtypes by Van Calker et al. (1979),
based on the ability of adenosine analogs to
inhibit or stimulate adenyl cyclase. Both
receptors are present in the central nervous
system (Daly, 1985; Fredholm, 1982). A1
adenosine receptors widely distribute in brain,
whereas A2 receptor sites are localised in
dopamine-rich brain areas such as striatum,
nucleus accumbens and olfactory tubercle (Bruns
et al., 1986). The striatum may be one of the
sites involved in yawning induced by drugs
(Yamada et
al., 1986). A1 and A2 adenosine receptors
are prescrit in the striatum, which has been
shown to regulate acetylcholine release (Brown
et al., 1990). Our previous work has shown that
the adenosine receptor antagonist, theophylline,
inhibits yawning behaviour in rats (Zarrindast
and Poursoltan, 1989; Zarrindast and Nasir,
1991).
In the present study, we have tested the
effects of adenosine receptor agonists on
yawning induced by the anticholisterase agent,
physostigmine. [...]
-
- Discussion In the present work, both
intracerebroventricular (i.c.v.) or
intraperitoneal (i.p.) administration of
thecholinesterase inhibitor, physostigmine,
induced dosedependent yawning. The response
induced by i.p. injection of the cholinergic
drug was decreased by both i.p. or i.c.v.
administration of the muscarinic receptor
antagonist, atropine. The data indicate that a
central cholinergic stimulation mechanism is
involved in physostigmine-induced yawning. This
is in agreement with a previous report that
activation of cholinergic mechanisms can induce
yawning (Zarrindast and Poursoltan, 1989).
Septal and striatal dopamine D2 receptors has
been suggested to be involved in yawning in rats
(Yamada et al., 1986). It has been also shown
that yawning induced by a doparmnergic mechanism
is mediated through cholinergic activation
(Carlsson, 1975; Di Chiara et al., 1976).
Accordingly, it can be suggested that septal and
striatal cholinergic systems are the sites of
physostigmine-induced yawning.
The prescrit results show that the adenosine
receptor agonists, N 6_CyClohexyladenosine (Moos
et al., 1985) and NECA (Heffner et al., 1989),
when administered either peripherally or
centrally, decreased the behaviour induced by a
cholinergic agent, physostigmine, suggesting
interactions of central adenosine mechanism(s)
with cholinergic-induced yawning
behavior.
- Adenosine actions have been detected at both
presynaptic and postsynaptic sites (Proctor and
Dunwiddie, 1983; Lee et al., 1984; Schubert and
Lee, 1986). Both adenosine A1 and A2 receptors
are present in the striatum, and are localized
to cholinergic nerve terminals. The former have
been shown to inhibit acetylcholine release. In
contrast, adenosine A2 receptor cause
stimulation of acetylcholine release (Richardson
and Brown, 1987; Brown et al., 1990). It has
been shown that N 6_cyclohexyladenosine and NECA
have affinity for both adenosine A, and A 2
receptors (Stone, 1985). Considering the
cholinergic nature of yawning induced by
physostigmine (Urba-Hoimgren et al., 1977;
Zarrindast and Poursoltan, 1989), a possibility
may exist that A1 activation by
N'-cyclohexyladenosine or NECA decreases the
release of acetylcholine and in turn reduces the
behaviour. The adenosine A1 receptor antagonist,
8-phenyltheophylline, did not alter the
physostigmine response, but prevented the
inhibition of the yawning induced by N
6_CyClohexyladenosine. This may support the
suggestion that adenosine A1 activation causes a
decrease in the cholinergic-induced
yawning.
-
- In contrast to 8-phenyltheophylline, the
adenosine receptor antagonist, theophylline,
decreased the yawning induced by physostigmine.
Theophylline has been proposed to be an
adenosine receptor antagonist (Bruns et al.,
1986) which may exert a greater A2 antagonist
effect (Ferre et al., 1991). Thus there is the
possibility that blockade of adenosine A2
receptors by theophylline decreased the release
of acetylcholine. This possibility is supported
by the finding of Brown et al. (1990) that A 2
stimulation is able to increase acetyl choline
release in the striatum. Since
N'-cyclohexyladenosine and NECA have no
selective affinity for adenosine A1 or A2
receptors (Stone, 1985), selective adenosine
receptor agonists may be needed to clarify the
exact mechanism involved. High doses of
theophylline inhibit phosphodiesterase;
considering that activation of adenosine A1
receptors decreases cAMP levels (Van Calker et
al., 1979), should stimulation of adenosine A1
receptors be responsible for inhibition of
yawning, the increase in cAMP caused by
theophylline cannot be part of the mechanism of
the effect on yawning.
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