CNS Pharmacology Department,
Oraganon, The Nederlands
A number of centrally active drugs were
tested for antagonism of physostigmine- or
apomorphine-induced yawning and for
apomorphine-induced penile erections. The alpha
2-adrenoceptor antagonists piperoxan and
idazoxan inhibited the yawning response without
affecting the penile erections. The 5HT agonist
quipazine and the histamine antagonist
dexchlorpheniramine inhibited the yawning
response more effectively than the penile
erections. Dexchlorpheniramine even enhanced the
apomorphine-induced penile erections and induced
penile erections in physostigmine-treated rats.
The 5HT antagonists metergoline and methysergide
blocked the apomorphine-induced penile erections
without affecting the yawning response. The
alpha 2-adrenoceptor agonist clonidine, the
dopamine antagonist sulpiride, the
antihistaminic mepyramine and the benzodiazepine
chlordiazepoxide inhibited both yawning and
penile erections at the same dose level. The
alpha1-adrenoceptor antagonists prazosin and
phenoxybenzamine were inactive. It is concluded
that yawning and penile erections can be
differentially affected by drug treatments.
Also, while concomitant yawning and penile
erections can be selectively induced by a class
of dopamine receptor agonists, the same
selectivity does not apply to antagonism of
these induced behaviours.
Introduction
It was previously reported that yawning
accompanied by an increase in penile erections,
is chacteristically elicited by many dopamine
agonists (Mogilnicka and Klimek, 1977;
Benassi-Benelli et al., 1979), in particular
those claimed to have selectivity for the
dopamine autoreceptor (Gower et al., 1984).
Cholinergic agents such as physostigmine also
cause yawning but do not elicit penile erections
(Urba-Holmgren et al., 1977; Gower et al.,
1984). A cholinergic-dopaminergic interaction
has been proposed to be involved in the
mediation of yawning (Yamada and Furukawa, 1980;
Gower et al., 1984; Ushijima et al., 1984).
While both yawning and penile erections are
similarly antagonized 1by centrally acting
dopamine antagonists and anticholinergics, there
is evidence that the two responses are
differentially influenced by other centrally
active drugs. For example, naloxone inhibits
drug-induced yawning but enhances the penile
erections elicited either by apomorphine
(Berendsen and Gower, 1983) or by
N-propylnorapomorphine (NPA) (Ferrari and
Baggio, 1982). The first aim of this
investigation was to obtain more evidence for
the selective drug sensitivity of yawning and.
penile erections. The second aim was to evaluate
whether antagonism of the yawning-erection
syndrome could be useful to identify drugs as
antagonists for the receptors involved in the
elicitation of these behavioural effects.
Discussion
The present study shows that while drue
induced yawning and penile erections have
certain pharmacological attributes in common the
responses could be separated in terms of the
effects of pretreatment with certain
antagonists. Thus the a2-adrenoceptor
antagonists piperoxan idazoxan selectively
inhibited yawning elicitec apomorphine or
physostigmine but had no effect on
apomorphine-induced penile erections. In
contrast, the 5HT antagonists, metergoline
methysergide selectively inhibited the penile
erections without affecting yawning. These
results report earlier work indicating an
involvement different neuronal mechanisms in the
two responses (Berendsen and Gower, 1983).
The effects of piperoxan and idazoxan imply
role for the a2-adrenoceptor in the elaboration
of yawning but not of penile erections. The
reley a-adrenoceptor appears to be specifically
a2 the alpha-antagonists prazosin and phenoxybe
mine were without effect. This is not a straight
ward involvement in the mediation of yawning
since clonidine, at doses activating the
a2-adrenoreceptor, did not itself elicit yawning
(Gower et 1984) but reduced drug-induced yawning
penile erections. The antagonism by clonidine
penile erections, induced either by NPA or
intraventricular ACTH, was also reported by
Baggio and Ferrari (1980) and Poggioli et al.
(19g
The antagonism of penile erections but
yawning by methysergide and metergoline ports an
exclusive role for serotonin in elaborating
penile erections. Similar selective effect
methysergide have already been described
Methygide blocked lisuride-induced penile
erections did not affect either lisuride- or
physos tigmine-induced yawning (Baggio and
Ferrari 1983, Yamada and Furukawa, 1981). The
involvement of serotonin cannot as yet be
interpreted as a straightforward mediation by a
serotonergic pathreway station between the
dopamine receptors the penile erection response
since quizapine a putative 5HT mimetic (Green et
al. 1976, Roríguez et al., 1973)
antagonized both yawning and penile erections.
It may be that different serotonin receptors
(Leysen et al., 1981) are involved in the
elicitation and in the antagonism of penile
erections. This is pertinent to the results of
studies by Ahlenius and Larsson (1984) showing
that 5-hydroxy-tryptophan depresses but the 5HT
agonist,
8-hydroxy-2-(di-n-propyl)amino-tetralin,
facilitates sexual behaviour.
The blockade by the atypical neuroleptic
sulpiride of apomorphine-induced yawning while
prostigmine-induced yawning was relatively
unchanged confirms previous findings (Dubuc et
al.,1982). It was found that sulpiride also
blocked penile erections ad in this respect
resembles the typical neuroleptic haloperidol
(Benassi-Benelli et al. 1979; Berendsen and
Gower, 1983).
The finding that dexchlorpheniramine induces
penile erections is intriguing in view of the
lack of such an effect with mepyramine. Both
drugs have antihistamine effect in common. This
observation is worth investigating further in
view of both the on use of the two compounds in
clinical practice and the interest in
understanding the mechanism of action of
induction of erections.
Mepyramine and dexchlorpheniramine and the
anxiolytic chlordiazepoxide reduced drug-induced
yawing. The sedative effects of these compounds
may have interferenced with yawning. This is
interesting because one might think that yawning
is corollary of the sedation induced by
apomorphine. It is also possible that these
drugs interfere with the motor execution of the
response. The effective dose of chlordiazepoxide
also causes muscle relaxation.
These results therefore reveal drug-induced
ing and penile erections as responses which
influenced by psychotropic drugs with diverse
mechanisms of action. Previously it has been
demonstrated that the yawning-erection syndrome
could be elicited by a group of dopamine
agonists, suggesting selectivity for a receptor
resembling the dopamine autoreceptor (Gower et
al., 1984). Such selectivity cannot be claimed
for the antagonism of yawning and erection
syndrome and therefore caution is indicated when
one is trying to use antagonism of
apomorphine-induced yawning erections as an
indication for blockade of the receptor
resembling the dopamine autoreceptor.
-Berendsen
HG Androgenic influences on
apomorphine-induced yawning in rats Behavioral
and neural biology 1981; 33; 123-128
-Berendsen
HG, Gower AJ Opiate influences on
drug-induced yawning in the rat Behav Neural
Biol. 1981; 33; 1; 123-128
-Berendsen
HG ; AJ Gower Opiate-androgen interactions
in drug-induced yawning and penile erections in
the rats Neuroendocrinology 1986; 42;
185-1901
-Berendsen
H et al Involvement of 5-HT1c-receptors in
drug-induced penile erections in rats
Psychopharmacology 1990; 101; 57-61
-Gower
AJ Effects of acetylcholine agonists and
antagonists on yawning and analgesia in the rat
Europ J Pharmacology 1987; 139; 79-89
