- Abstract:
-
- 1. The report examines the temporal sequence
of yawns induced by apomorphine and whether the
opiate antagonist, naloxone, affects it.
-
- 2. Before administering apomorphine (0.075
mg/kg) or saline, rats (n8) were pretreated with
naloxone (1 mg/kg) or saline. Each subject
received all 4 possible treatmants
(saline-saline, saline-apomorphine,
naloxone-saline, and naloxone-apomorphine) in
random order.
-
- 3. Results indicate that yawning induced by
apomorphine seems to come in fits; that is,
there is a series of yawns spaced closely
together and followed by a period of quiescence
before the start of another cluster of
yawns.
-
- 4. Naloxone reduced the number of
apomorphine-induced yawns, and the occurrence of
very short inter-yawn intervals.
-
- 5. It is suggested that the timing of yawns
tray provide useful information regarding some
pathologies and that opiates may potentiate the
action of dopaminergic systems.
-
- Introduction
-
- During the course of a study on the
interaction of dopaminergic and opiate systems
(Szechtman, submitted), I observed that after an
injection of apomorphine, yawning in rats
appears to come in clusters; that is, a series
of yawns with short inter-yawn intervals, a
period of quiescence, and then another fit of
yawns. While the induction of yawning by low
doses of apomorphine is well known (Dubuc et
al., 1982; Holmgren and Urba-Holmgren, 1980; Lal
et al., 1979; Mogilnicka and Klirnek, 1977;
Nickolson and Berendsen, 1980; Serra et al.,
1983; Yamada and Furukawa, 1980), the temporal
characteristics of this response have not been
documented. The purpose of this preliminary
report is to draw attention to the seemingly
non-random nature of the timing of yawns. In
addition to apomorphine-induced yawning, data
are presented showing that pretreatnent with
naloxone alters their timing, reducing the
occurrence of very short inter-yawn
intervals.
-
- Discussion
-
- There is a popular saying that "one yawn
brings seven". Indeed, although he did not
provide any data, Barbizet (1958) wrote that in
humans "...a yawn is rarely isolated. It usually
occurs in fits of two or three. The intensity of
the yawn often increases, and each yawn is
separated by a few regular breaths. Sometimes,
the yawn will be repeated, irregularly, during
several minutes." This report provides empirical
support for this statement by shading that in
rats after an injection of apomorphine, yawns
seem to come in clusters. Furthermore,
pretreatment with naloxone seems to alter the
timing of yawns within a cluster, especially the
occurrence of very short inter-yawn intervals.
Because yawning is often associated with certain
pathologies (reviewed by Barbizet, 1958;
Heusner, 1946; Lehmann, 1979), the alteration in
timing of yawns may prove useful as a
differential indicator of sone of these disease
states.
-
- The fact that yawns come in fits suggests
elements of positive feedback in the circuits
mediating this response. The finding that the
opiate antagonist, naloxone, reduces the very
short inter-yawn intervals, suggests that
endogenous opiates may he released during
apomorphine-induced yawning and potentiate the
action of dopaminergic system in this response.
1975) and emesis in dogs, would support the
concept that lisuride has mainly central
DA-activity, as suggested by Horowski and
Wachtel (1976).
-
- PE elicited by lisuride in rats was
antagonized by both DA and 5-HT antagonists,
rendering a simple interpretation
difficult.
-
- The antagonism might be non-specific and not
exerted at the same receptor site, especially
given the above mentioned, mild activation of PE
by lisuride, in comparison with that obtained
with other typical dopaminomimetics. On the
other hand, the supposed dopaminergic nature of
SY was confirmed by the clear antagonism
obtained with haloperidol and sulpiride and by
the failure of methysergide. Haloperidol,
classically considered a dopamine antagonist
drug, exerts its activity on pre- and
post-synaptic DA-receptors (Long et al. 1975;
Lokhandwala and Buckley 1977). Sulpiride seems
also to be a specific DA-receptor antagonist
with particular affinity for presynaptically
located DA-receptors involved in the inhibition
of DA-synthesis and release, the so-called
autoinhibitor-receptors (Kehr et al. 1972;
Carlsson 1975; Bunney and Aghajanian 1975; Di
Chiara et al. 1976; Corsini et al. 1979; Spano
et al. 1979).
-
- Although detailed studies must obviously be
undertaken on the biochemical changes in
neurotransmission correlated with SY, our data
suggest that this behavior might be an
expression of a preferential
DAautoreceptor-stimulation. It must be stressed
that we observed that the low doses of lisuride
which elicitSYsimultaneously induced sedation
(that is, a considerable reduction in
spontaneous locomotor activity-data not
reported). This is in agreement with the
behavioral effects of low doses of typical
DA-stimulants such as APO and N PA, which elicit
SY (Benassi-Benelli and Ferrari 1979;
Benassi-Benelli et al. 1979) and sedation both
in animals and in man (Di Chiara et al. 1976;
Corsini et al. 1977a, b; Spano et al. 1979),
simultaneously inhibiting dopaminergic firing
and DA-synthesis in the caudate nucleus and
nucleus accumbens, presumably through
preferential activation of presynaptic
receptors, as assessed by changes in DOPAC
levels (Serra et al. 1981). Moreover, lisuride
is also reported to reduce DA turnover and
synthesis at low doses (Kehr 1977).
-
- In conclusion, our behavioural findings
strongly support an effect of lisuride on
dopaminergic mechanisms. At low doses it
probably has a preferential affinity for
presynaptic inhibitor receptors, the activation
of which leads to SY and, probably, to PE
enhancement. At higher doses it would appear to
have chiefly an agonistic effect on the
postsynaptic DA-receptors, thereby eliciting SB.
1f this hypothesis is confirmed by biochemical
studies, induction of SY in addition to sedation
could be used as a simple and sensitive
behavioral model for testing drugs acting on
presynaptic autoinhibitory DA-receptors.
Whatever the type of receptor involved, we
should like to stress that SY, specifically
stimulated by dopamine agonists, would seem to
be a parameter worthy of attention in studying
animal behavior.
- -Szechtman
H et al Sensitization and tolerance to
apomorphine in men: yawning, growth hormone,
nausea, and hyperthermia Psychiatry Research
1988, 23, 245-255
- -Szechtman
H Timing of yawns induced by a small dose of
apomorphine and its alteration by naloxone Prog
Neuro-Psychopharmacol & Biol Psychiat 1984;
8; 743-746
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