Introduction Yawning behaviour is a
curious and still little understood response
which is induced in many vertebrate species
(Baenninger
1987). The most widely held hypothesis is
that yawning serves as a form of respiration
induced by high levels of carbon dioxide in the
blood. At least in humans, it has been shown
that neither oxygen nor carbon dioxide levels
contribute to yawning rates (Provine
et al. 1987).
Yawning can be elicited in experimental
animals by a number of dopamine agonists
including apomorphine and bromocriptine
(Mogilnicka and
Klimek 1977; Baggio and Ferrari 1983;
Zarrindast
and Poursoltan 1989). The involvement of central
cholinergic mechanisms in the behaviour has also
been suggested (Urba-Holmgren
et al. 1977; Yamada
and Furukawa 1980; Ushijima
et al. 1984; Zarrindast and Poursoltan
1989). Our previous experiments showed that the
yawning produced by dopminergic or cholinergic
agents was inhibited by the adenosine receptor
antagonist theophylline (Zarrindast and
Poursoltan 1989). We also found that a central
adenosine mechanism interacts with physostigmine
induced yawning (Zarrindast et al. 1995). Septal
and striatal dopamine receptors have been
proposed to be involved in yawning behaviour in
rats (Yamada et al. 1986). The behaviour seems
to be mediated through D2 dopamine receptors in
rats (Protais
et al. 1983; Gower
et al. 1984; Longoni et al. 1987, Zarrindast
and Poursoltan 1989). Interactions between
adenosine and the dopaminergic system (Brown et
al. 1991) and adenosine with the D2 dopamine
mechanism have also been shown (Murayama et al.
1990).
In the present study, the effects of
adenosine agents on yawning induced by
apomorphine have been investigated.
Discussion
In the present work, both SC and ICV
injections of apomorphine induced dose-dependent
yawning. This is in agreement with previous
reports that peripherally (Dourish
et al. 1985; Zarrindast and Poursoltan 1989)
or centrally administered apomorphine into areas
such as caudate nucleus (Dourish et al. 1985),
septum and the paraventricular nucleus
(Melis et al.
1987) can induce this behaviour and that central
dopaminergic system (Urba-Holmgren
et al. 1982) may be related to the display
of yawning behaviour. However, the behaviour can
also be induced by cholinergic agents
(Urba-Holmgren et al. 1977; Yamada and Furukawa
1980, Ushijima et al. 1984; Zarrindast and
Poursoltan 1989). Our previous experiments
(Zarrindast et al. 1995) showed that
physostigmine-induced yawning was reduced by
adenosine drugs. The purpose of this study
was to focus on the influence of adenosine
agonists and antagonists on apomorphine-induced
yawning. The behaviour bas also been proposed to
be centrally mediated (Dourish and Huston 1985)
and due to septal and striatal D2 receptor
activation (Yamada et al. 1986). Adenosine has
been shown to function as a neuromodulator or a
neurotransmitter in many areas of the mammalian
CNS (Phillis and Wu 1981; Snyder 1985). There
are at least two types of adenosine receptor
subtypes; the A1 adenosine receptors inhibit
adenylyl cyclase whereas the A2 adenosine
receptors stimulate adenylyl cyclase (for review
sec Stiles 1986, Fredholm and Dunwiddie 1988).
Both A1 and A2 adenosine receptors are present
in striatum.
The presen results indicate that adenosine
agonists NECA (Heffner et al. 1989) and CHA
(Moos et al. 1985) have the capability to reduce
the yawning induced by apomorphine dose
dependently. These data suggest that
adenosine receptor activation exerts a
negative influence on the apomorphine-induced
yawning behaviour. The results may support
those of others (Murayama et al. 1990, Brown et
al. 1991) that suggest interaction between
adenosine and dopaminergic mechanisms. It has
been shown that NECA have affinity for both
adenosine A1 and A2 receptors (Stone 1985).
Although, the drug has been shown to have more
affinity for A2 then A1 adenosine receptor
subtypes (Heffner et al. 1989). CHA has been
shown to be a selective and potent A1 adenosine
agonist (Moos et al. 1985). Since the A1
adenosine antagonist 8-PT (Smellie et al. 1979;
Jacobson et al. 1985) decreased the inhibitory
effect of both drugs, the response induced by
the both adenosine agonists seems to be mediated
through the activation of the adenosine A2
receptor mechanism. 8-PT by itself did not alter
apomorphine induced yawning, suggesting that
there is no active negative influence of A1
adenosine on yawning.
The present data showed that, in contrast to
8-PT, theophylline decreased yawning induced
by apomorphine. Our previous studies have
shown that theophylline reduced several
behaviours, such as yawning induced by
dopaminergic and cholinergic drugs (Zarrindast
and Poursoltan 1989), pecking induced by
apomorphine in chickens (Zarrindast and Nasir
1991) and catalepsy induced by NECA or CHA
(Zarrindast et al. 1993). 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). The
possibility may exist that blocking the A2
adenosine receptor unmasks A1 receptor subtype
and in turn, elicits inhibition of
apomorphine-induced yawning.
Theophylline is a phosphodiesterase
inhibitor. Since the A1 adenosine agonist CHA,
which decreases cAMP, also attenuates the
behaviour, the inhibition of yawning through an
increase in cAMP levels seems unlikely.
Methylxanthines have also been proposed to have
direct dopaminergic properties (Wanatabe and
Uramboto 1986, Herrera-Marschitz et al. 1988,
Casas et al. 1989), and they may also release
catecholamines (Lin et al. 1980). Since other
behaviours, such as pecking in chickens
(Zarrindast and Namdari 1992), and licking in
rats (Zarrindast et al. 1992) which are induced
by D1/D2 dopaminergic systems, are attenuated by
theophylline (Zarrindast and Nasir 1991;
Zarrindast and Sharifzadeh 1995), the
dopaminergic mechanism of theophylline cannot be
included. However, to clarify the exact
mechanism involved, more studies are required.
