Introduction : Yawning is a
physiological response which is associated with
fatigue and recovery from stress. A number of
dopamine agonists including apomorphine and
bromocriptine elicited yawning behaviour in
rats. It has been proposed that this behaviour
is mediated via a D2 dopamine autoreceptor.
Central cholinoceptor activation by
physostigmine or pilocarpine also induces
yawning. The yawning induced by dopamine
agonists and agents acting on cholinoceptors are
inhibited by muscarinic antagonists, such as
scopolamine and atropine. These studies suggest
that dopamine receptor agonists induce yawning
by activation of the cholinergic system. Links
between acetylcholine and dopaminergic neurones
have been described in the septohippocampal
system and the striatum and it has been shown
that stimulation and lesion of these structures
affect yawning. It has also been suggested that
dopamine agonists elicit yawning by stimulating
dopamine D2 receptors within these
structures.
Opiate interactions with both dopaminergic
and cholinergic systems have been demonstrated.
There appears to be a close association between
opiate receptors and dopaminergic cell bodies
and nerve endings in the substantia nigra and
striatum. Morphine, methadone and other opiates
modulate dopaminergic neurotransmission in
mesolimbic and nigrostriatal projections. Opiate
agonists also inhibit the release of
acetylcholine in the central nervous system, an
effect which is antagonized by naloxone.
In the present study, we have evaluated the
effect of morphine on yawning induced by
dopaminergic and cholinergic activation.
[...]
Discussion :It has been proposed that
yawning induced by low doses of dopamine
receptor a gonists is due to activation of D2
receptors, although D1 receptors may be involved
in yawning induced by apomorphine. The yawning
induced by dopamine agonists appears to be
mediated via a cholinergic mechanism, since it
is inhibited by muscarinic receptor
blockade
Although dopaminergic and cholinergic
interactions have been described at various
anatomical sites within the brain, the locus of
the interaction with respect to yawning
behaviour has not been established, although it
has been démonstrated that intact
nigrostriatal projections are required for drugs
acting on dopamine receptors to induce yawning.
In the present study bromocryptine induced
yawning was inhibited in a naloxonesensitive
manner by morphine. Although the nigro-striatal
pathway has been shown to be regulated by µ
and ¶ opioid receptors in both the striatum and
the substantia nigra, such a mechanism is
unlikely to explain the present results since
morphine in a similar dose range also inhibited
cholinoceptor-mediated yawning.
Although morphine is able to inhibit the
release of acetyl choline in the central nervous
system in a naloxone-sensitive manner such a
mechanisrn is unlikely to explain the present
results since morphine was able to inhibit the
yawning induced by the direct acting
cholinoceptor agonist, as weil as that induced
by physostiginine.
We have previously demonstrated that yawning
induced by bromocriptine and physostigmine are
decreased by theophyl- line (Zârrindast
& Poursoltan, l989). Theophylline is an
adenosine receptor antagonist and a
phosphodiesterase inhibitor which increases
intracellular adenosine 3',5'-cyclic
monophosphate (cyclic AMP) concentrations, and
may also release dopamine. However, a similar
mechanism is unlikely to explain the present
effects since morphine bas been reported to
stimulate adenosine release.
The most likely explanation of the present
findings is that morphine inhibits yawning
induced by dopamine agonists and drugs acting at
cholinoceptors at an opioid site downstrearn
from both the dopamine receptors- and
cholinoceptors. The weak but dose-dependent
induction of yawning by naloxone suggests that
endogenous opioids may mediate a tonic
inhibitory effect on yawning behaviour.
-Melis MR et
al. Prevention by morphine of apomorphine-
and oxytocin-induced penile erection and
yawning: involvement of nitric oxide
Naunyn-Schmiedeberg's arch Pharmacol 1997; 600;
355-595
-Zarrindast
MR, Poursoltan M Interactions of drugs
acting on central dopamine receptors and
cholinoceptors on yawning responses in the rat
induced by apomorphine, bromocriptine or
physostigmine Br J Pharmacol 1989; 96; 4;
843-848
-Zarrindast,
MR, Jamshidzadeh A Inhibitory effect of
morphine on yawning induced by cholinoceptor and
dopamine D2 receptor activation in rats Br J
Pharmacol 1992; 105; 3; 675-8
-Zarrindast
MR, Toloui V, Hashemi B Effects of GABAergic
drugs on physostigmine-induced yawning in rats;
Psychopharmacology (Berl) 1995; 122; ;
:297-300
