- 1. Introduction The effects of the
central administration of bombesin (BN) have
been documented for a variety of behaviors
(Kulkosky et al., 1982; Cowan et al., 1985).
Some of the most conspicuous are vigorous
scratching (Brown et al., 1977), excessive
grooming and wet-dog shaking (Gmerek and Cowan,
1981). BN also stimulates dose-dependent
elevations in plasma adrenocorticotrophic
hormone (ACTH), corticosterone, catecholamines
and glucose (Brown et al., 1979, 1988; Gunion et
al., 1989; Plamondon and Merali, 1993, 1997;
Malendowicz and Nussdorfer, 1995). These
findings have led to suggest that BN-like
peptides play a role in the mediation of the
stress response (Kent et al., 1998).
-
- The behavioral reactions to mild stress,
however, include not only excessive grooming but
also other behaviors such as yawning
(Delius,
1967, 1988; Dourish
and Cooper, 1990). Yet, there are few
reports onthe relation between BN and yawning
(Kulkosky et al., 1988) which could indicate
whether BN has different behavioral correlates
from other peptides involved in the stress
response. Indeed, peptides such as ACTH, whose
link to stress is well established (Akil and
Moreno, 1995), elicit grooming and yawning
(Gispen and Isaacson, 1981; Argiolas
and Melis, 1998). The lack of such studies
is partly because yawning occurs spontaneously
at a very low frequency, making it difficult to
appreciate little variations that may otherwise,
indicate meaningful changes.
-
- We have in our laboratory two strains of
SpragueÐDawley
rats that were selectively bred for high-yawning
(HY) and low-yawning (LY) frequency (Urba-Holmgren
et al., 1990). The strains also differ in
other behaviors. For example, HY rats circulate
in an open field arena and groom in a novel
environment more than LY rats (Moyaho
et al., 1995; Eguibar
and Moyaho, 1997). The fine structure of
water-induced grooming is also different between
both strains: LY rats show sequences that are
more stereotyped than those of HY rats (Moyaho
et al., 1995). In addition, HY rats yawn more
than LY rats after the administration of
cholinesterase inhibitors and dopamine receptor
agonists (Urba-Holmgren
et al., 1993). Thus, the unusual
characteristics of these strains make it
interesting to study the behavioral correlates
of BN administration in these rats. This might
contribute to our understanding of the potential
role of the BN-related peptides in the stress
response.
-
- The present study assessed the effects of
centrally administered BN on yawning and
grooming in HY rats. The study included the
analysis of other behaviors that commonly
correlate with yawning or grooming. Because of
the number of behaviors recorded, we analysed
the data with multivariate methods as
recommended by Stahle and Wold (1988) to avoid
misinterpretation of results. LY strain was also
used for comparative purposes.
[...]
-
- 4. Discussion This is the first study
that reports a significant inhibition of yawning
by the central administration of BN. The result
could not be only attributed to a peculiarity of
HY rats, for PCA showed a diminution of yawning
even in LY rats.
- Although earlier studies had described the
behavioral effects of BN and its difference from
other peptides with stimulating effects on
grooming, they scarcely mentioned yawning
(Kulkosky et al., 1982; Gmerek and Cowan, 1983).
This probably was because the spontaneous
frequency of this behavior was too low for
detecting a significant decrease. In addition,
those data were analysed with univariate
methods, which are not sensitive, as PCA is, to
qualitative changes of behavior. PCA showed the
dynamic effect of BN on HYand LY rats'
behavior.
- BN-treated rats yawned 2Ð3 h after the
beginning of the experiments (data not shown).
The frequency of response did not seem to differ
from that of control animals, so that BN
administration displaced yawning. This finding
suggests that BN affects the length of the
initial response to novel environments. In this
respect, BN differs from other peptides such as
oxytocin and ACTH which equally increase
grooming and yawning (Ferrari et al., 1963;
Gispen et al., 1975), and therefore the entire
response to novel environments. Grooming and
yawning, however, are not exclusively
connected with novelty. Grooming may serve
several functions: from cleaning the fur to the
spread of chemical substances or as a
displacement activity (for a review, see Spruijt
et al., 1992).
-
- Yawning, apart from its relation to stress,
has been associated with transitions between
sleep and waking, with threats and conflict, and
with boredom and sleepiness (Provine
et al., 1987; Baenninger,
1997). Therefore, the effect of BN on
grooming and yawning could be linked with other
functions. Stress, on the other hand, may
involve the activation of a feed-forward system
to mobilize the central nervous system (Koob,
1999). Thus, the behavioral responses to stress
may not be straightforward so that HY rats might
groom vigorously because of skin irritation. Our
findings, though, are more consistent with the
view that grooming is a way to reduce arousal
(Gispen and Isaacson, 1981), for BN
administration correlates with elevations in
stress-related substances (Kent et al., 1998,
2001). PCA showed that BN produced a qualitative
change from yawning to grooming that varied in a
strain-specific manner.
-
- While in HY rats penile erections and
stretching of the body dominated part of the
variation explained by PC2, in LY rats the
corresponding variation, although of lower load,
was due to the frequency and duration of
grooming-independent scratching. Therefore BN at
certain doses seems to favour a kind of
'arousal' component in HY rats, whereas in LY
rats predominates a response more like that
reported by previous studies (Brown et al.,
1977). Besides confirming a straindependent
effect, this finding is remarkable because given
the positive correlation between yawning and
penile erection in HY rats (Holmgren
et al., 1985), it would have been expected
both responses to change in the same
direction.
- This raises the possibility that BN-like
peptides may be involved in the functional
association between yawning and penile erection.
It is timely to mention that the separation
between animals receiving 0.1 mg and those
challenged with 1.0 mg is more apparent in HY
rats than in LY rats. Yet, the application of
other doses between 0.005 mg and 0.1 mg would
have not changed so much the picture, as they
would have lain in the centre of the principal
component ordinates, and hence with little
contribution to the components.
-
- The variation due to PC3 (data not shown) in
HY rats arose from scratching that occurred
independent of grooming episodes, whereas in LY
rats it resulted from scratching within grooming
bouts. Accordingly, BN did not affect scratching
duration within grooming bouts in HY rats , so
that this peptide seems to discriminate between
apparently two types of scratching.
Interestingly, this behavior occurs more
frequently in HY than in LY rats after exposure
to a novel environment. Although scratching was
not divided in that study (Eguġibar
and Moyaho, 1997), there is the possibility
that the time sampling method used for recording
it (Gispen and Isaacson, 1981) had not
distinguished between categories. In other
words, that part of the scores corresponded to
scratches occurring separated from grooming
sequences.
-
- This presumption and the present data
suggest that there could be two subsystems of
scratching. The differential effect of the
central administration of BN on them indicates
that it is likely that they depend on different
neurochemical mechanisms and neural substrates.
Although previous evidence suggests that
vigorous scratching after BN does not reflect a
direct response to skin irritation (Gmerek and
Cowan, 1983), there remains the possibility that
scratching independent of grooming episodes does
result from changes in skin sensation as has
been suggested by previous studies (Gmerek and
Cowan, 1981; Cowan et al., 1985). Perhaps,
scratches independent of grooming sequences
depend directly on a spinal command, while those
within grooming are modulated by higher brain
centres. Indeed, it is known that such centres
may inhibit the activity of the generator for
scratching (Gelfand et al., 1988).
-
- Since some of the behavioral effects of BN
seem to depend on intact muscarinic cholinergic
activity (Kulkosky et al., 1988), a plausible
explanation of the differential effects of this
peptide on HY and LY rats' behaviors is that the
former strain might have a higher cholinergic
tone than he latter, as has been suggested
(Urba-Holmgren et
al.,1993). However, preliminary results have
also indicated that the dopaminergic
transmission may be involved in HY and LY rats
behavioral differences. Therefore, both
cholinergic and dopaminergic systems may
contribute to the differences between HY and LY
rats. Alternatively, the differential effects of
BN on HY and LY rats might reflect differences
in sensitivity of the two subtypes of receptors
(Battey and Wada, 1991) to BN. Further studies
are necessary to tease apart these
possibilities.
-
- In summary, the inhibition of yawning
with BN enhances the initial response to novel
environments by increasing grooming. The
findings support the suggestion that BN-like
peptides in the central nervous system of
mammals might modulate the neurochemical
correlates of the restorative behavioral actions
to face stress situations. BN also appears to
differentiate between two subsystems of
scratching. If so, these findings would be
potentially relevant to further study what the
function of these subsystems is.
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