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mise à jour du
4 décembre 2003
Pharmacology, Biochemistry and Behavior
2002; 71; 2002; 103-109
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Bombesin decreases yawning in a high-yawning subline of SpragueÐDawley rats
Diaz-Romero M, Eguibar JR, Moyaho A
Benemérita Universidad Autonoma de Puebla
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren

Chat-logomini

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.