mise à jour du
18 novembre 2004
2004; 38; 283-288
Genotype-dependent effect of ACTH 1-24 on grooming and yawning in two inbred strains of rats
Jose R. Eguibar, M. Barajas, A Moyaho
Instituto de Fisiolog§a , Benemerita Universidad Autonoma de Puebla, Mexico
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren


It has long been known that the intracerebroventricular administration of ACTH1-24 increases the duration of grooming episodes and the frequency of yawning in rats. The objective of this study was to investigate in what way these episodes are prolonged andwhether and to what extent genotype influences such effects. We compared the effect of increasing doses of intracerebroventricularinjections of ACTH1-24 on grooming and yawning in males of two inbred strains of SpragueÐDawley rats with distinct yawningfrequency, high-yawning (HY) and low-yawning (LY). In LY rats the duration of grooming episodes increased, while in HY ratsgrooming episodes augmented both in number and duration. In LY rats the duration of grooming components increased likewise, inHY rats however, neither the number nor the duration of the components changed. The grooming rate in both strains of rats wasslowed, though more so in LY than in HY rats. Yawning increased in LY rats but not in HY rats. We conclude therefore thatACTH1-24 increases the duration of grooming episodes by slowing the grooming rate according to genotype, and may or may notalter the frequency of yawning.
The intracerebroventricular (ICV) administration of ACTH1-24 prolongs grooming in rodents without affecting the number of episodes of this behaviour (Gispenand Isaacson, 1981). The exact nature of the way grooming episodes become longer has not yet been identified (but see Bressers et al., 1995; Gispen and Isaacson, 1981; Spruijt et al., 1992; van Wimersma Greidanus et al., 1985).
ACTH1-24 could either increase the number of grooming components per episode, make grooming components longer or affect both number and duration of grooming components. A study to distinguish between these alternatives would help us to understand better the role of ACTH1-24 in grooming behaviour. Since it is unlikely that following the administration of ACTH1-24, rats can simultaneously groom faster and longer, we hypothesize that ACTH1-24 slows grooming rate, i.e., rats spend more time grooming each part of their body. Besides the effect on grooming, the ICV administration of ACTH1-24 produces yawning (Ferrari, 1958;Ferrari et al., 1963).
Both grooming and yawning are stereotyped behaviours (Fentress, 1988; Dourish andCooper, 1990) and hence they might have a strong genetic component. A comparative study using inbred strains of rats, which differ in yawning and grooming may indicate the extent to which the effect of ACTH1-24 on these behaviours is genetically dependent. In this study, we have attempted to determine in what way grooming episodes are prolonged after the ICV administration of ACTH1-24 and evaluate the extent to which the response to ACTH1-24 is affected by genotype. To this purpose, we used two strains of SpragueÐDawley rats, previously selected for high- (HY) and low-yawning (LY) frequencies (Urba-Holmgren et al.1990). They have been shown to differ in novelty-induced grooming as well (Eguibar and Moyaho1997).
The purpose of the present study was an in-depthanalysis of the prolonging effect of ACTH1-24 ongrooming behaviour. In LY rats results corroborate theoutcome of former studies (Gispen and Isaacson, 1981) that ACTH1-24 increases the duration but not the number of grooming episodes, and show that this iscaused by a longer duration of the components of grooming behaviour. In HY rats, in comparison, bothduration and number were increased. This is an unusual effect of ACTH1-24, which can be attributed to genetic differences between HY and LY rats, but whose specificmechanisms are beyond this study. Similarly, the durationof grooming components after the administrationof ACTH1-24 differed between LY and HY rats: HY groomed each part of their body for a shorter time.
Previous studies suggest that such differential response might be due to the fact that HY rats interrupt systematicallytheir ongoing activities (e.g., grooming,resting, mating), and that they can hardly complete anorderly sequence of behaviour (Moyaho et al., 1995). Accordingly, these rats might be classified as rats with an attention deficit, but additional research is required to support this hypothesis. Administration of ACTH1-24 augmented yawning frequency in LY rats, which is consistent with previous reports on other animals (Argiolas et al., 2000; Ferrari,1958; Poggioli et al., 1995). However, ACTH1-24 did notaffect yawning in HY rats. This difference cannot be attributed to a ceiling effect since there are other drugs (e.g., colinomimetics and dopamine-receptor stimulants) that greatly increase yawning in HY rats (Eguibar and Moyaho, 1997; Eguibar et al., 2003; Urba-Holmgren et al., 1993). It seems instead that there is a maximum level above which ACTH1-24 does not increase yawning in HY rats. This finding is very interesting because no drug with inductive effects on yawning has failed to increase the frequency in HY rats. That yawning could have appeared as a rebound effect after the 120 min of observation is improbable, judging the trend of response to increasing doses of ACTH1-24, and data from previous reports (Argiolas et al., 2000).
Another explanation of the insensitivity of yawning to the administration of the drug could be a lack of receptors, but since ACTH1-24 did indeed affect grooming, distinct types of ACTH1-24 receptors might be involved in yawning and grooming. There are several subtypes of melanocortin receptors in the brain area (De Wied, 1999; Wikberg et al., 2000), of which the MC4 type is involved in both behaviours (Adan et al., 1994; Adan and Gispen, 2000; Argiolas et al., 2000; Vergoni et al., 1998). Yet, the fact that yawning occurs after a delay while grooming responds promptly (results not presented), suggests that different melanocortin receptors might be implicated. Since ACTH1-24 requires the activation of dopamine receptors (Guild and Dunn, 1982), an alternative explanation for the differential effect on HY and LY rats could be that they differ in dopamine neurotransmission. In addition to dopamine, other neurotransmitters are involved in ACTH-induced yawning, for example acetylcholine,opioïd peptides, Ca2+ ions and nitric oxide (for a review see Argiolas and Melis, 1998).
Accordingly, ACTH-induced yawning is prevented by muscarinic receptor antagonists (Yamada and Furukawa, 1980), bymorphine (Bertolini and Gessa, 1981), by x-conotoxin or organic Ca2+ channel blockers (Argiolas et al., 1990; Poggioli et al., 1993) and by nitric oxide synthase inhibitors(Melis and Argiolas, 1997). Therefore, differences in yawning frequency between HY and LY rats can also result from an interaction between ACTH1-24 and other neurotransmitter systems. Preliminary results from our laboratory indicate that indeed dopamine levels in the nucleus accumbens are higher in LY than inHY rats.
The diminution of the grooming rate suggests that ACTH1-24 affects or interacts with neural circuits involvedin ''recurrent routines'' as it produces repetitive sequences of behaviour. This effect resembles behaviour related to obsessiveÐcompulsive disorder in humans in which patients are unable to stop doing certain behaviours (e.g., washing, dressing or other toileting behaviours (Swedo, 1989). Patients lack a sense of confidence that leads them to checking until ''reaching satisfaction''(Insel and Pickar, 1983).
Neuropeptides have indeed been involved in obsessiveÐcompulsive behaviours (Sandyk,1987; but see Insel and Pickar, 1983). In addition grooming is displacement behaviour (Cohen and Price,1979) and displacement behaviours have been proposed for modelling obsessiveÐcompulsive disorder. Therefore, the effect of ACTH1-24 on grooming may be useful to understanding recurrent pathological behaviours.
In conclusion, these findings show that ACTH1-24 prolongs duration of grooming episodes by slowing the grooming rate. Such effect depends on genotype and may originate strain differences.
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