Timing of
yawns induced by a small dose of apomorphine and
its alteration by naloxone
Henry Szechtman
Department of Neurosciences,
University Hamilton, Ontario, Canada
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 (n=8) were pretreated
with naloxone (1 mg/kg) or saline. Each subject
received all 4 possible treatments
(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
may 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 Klimek, 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 pretreatment with
naloxone alters their timing, reducing the
occurrence of very short inter-yawn
intervals.
Methods
Animals Subjects used in this study were 8
male Sprague Dawley rats (440-550 g), housed 2
per cage in a colony with lights on from 0700 to
1900 hr. They were well habituated to testing
environment and drug injections because of an
earlier study (Szechtman, 1983) in which they
experienced 7 injections of apomorphine (0.15 -
1.25 mg/kg) in the same apparatus as used
presently.
Drugs. Naloxone hydrochloride was dissolved
in saline (I mg/ml) and apomorphine
hydrochloride in saline (2.5 mg/mi) plus 0.1%
ascorbic acid. Naloxone was injected
intraperitoneally and apatorphire was injected
subcutaneously under the scruff of the
neck.
Apparatus. Each rat was tested in a low
plastic done, 9 an high and 27 cm in dianter,
which rested on a glass floor. A mirror,
inclined 45° to it, permitted a bottcsi
view of the rat's behaviour which was recorded
continuously on a video cassette recorder
interfaced with a time-code generator.
Experimental Procedure Twenty minutes before
the start of testing, the subject was put into a
holding bowl for adaptation. Five minutes before
testing, it was injected with naloxone (1 mg/kg)
or saline. immediately before being transferred
to the testing apparatus, it received an
injection of apomorphine (0.075 mg/kg) or
saline. Each rat received all 4 possible
treatments (saline-saline, saline-apanorphine,
nsloxone-saline, and naloxone-apomorphine) in
random order. Tests were 30 minutes in duration,
conducted during light-on hours and spaced 2-3
days apart. The tine of occurrence of each yawn
was noted during playback of video records.
Statistical Analysis The frequency
distributions of inter-yawn intervals following
treatments with saline-apomorphine and
naloxone-apomorphine were compared using the
Kolmogorov-Snirnov two-sample test (Siegel,
1956)
Results
Figure 1 presents the record of yawns
exhibited by each rat following treatments with
saline-saline, saline-apomorphine,
naloxone-saline, and naloxone-apomorphine (there
was no yawning following injection of
rmloxone-saline). Inspection of this figure
suggests that yawning occurs in clusters; that
is, several successive yawns with short
inter-yawn intervals are followed by a
relatively long inter-yawn interval and another
grouping of yawns with short intervals between
them. While this report does not provide a
forcal analysis of the data, the figure does
convey a clear impression of such
clusterings.
The distribution of inter-yawn intervals for
the two most effective treatments, that is,
saline-apomorphine, and naloxomo-apomorphine, is
shown in Figure 2. It can be seen that yawns may
be spaced as close as 5 sec, of each other,
especially after treatment with
saline-apomorphine. Pretreatment with naloxone,
reduced not only the total member of yawns
during the 30 min. test (p < .01; see
Szechtman, submitted, for details) but also the
relative member of short inter-yawn intervals.
The latter observation is supported by the
Kolmogorov-Smirnov test which was used to
compare the frequency distributions of
inter-yawn intervals following treatments with
apomorphine and naloxone plus apomorphine. It
indicated a significant (p < .05) D vadslue
at the lower ends of the distributions.
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 showing that in
rats after an injection of apomorphine, yawns
seem to come in clusters. Furthermore,
pretreatment with naloxone seem 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 some 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 be released during
apomorphine-induced yawning and potentiate the
action of dopaminergic system in this
response.
