Intracerebroventricular ACTH activates the pituitary-adrenal system:dissociation from a behavioral response.

In the rat, intracerebroventricular injection of synthetic ACTH (ACTH_1–24, ACTH_1–16) elevated plasma corticosterone levels and induced the display of excessive grooming behavior. The grooming response could be elicited in hypophysectomized rats without concommittant elevation of plasma corticosterone. In intact rats subcutaneous injection of ACTH_1–24 and not of ACTH_1–16-NH₂ stimulated the release of adrenal corticosteroids, whereas no excessive grooming was observed. In contrast to the reduced effectiveness of a second icv injection of ACTH in inducing the behavioral response, no single-dose tolerance was observed for the effect of icv ACTH on the pituitary-adrenal system. Therefore it was concluded that two different central mechanisms underly the observed responses to the icv applied ACTH.     

ACTH acts via an anterior ventral third ventricular site to elicit grooming behavior

Intracerebroventricular but not parenteral application of ACTH has been shown to elicit excessive grooming behavior in rats and mice. This behavior is elicited by administration of ACTH into the lateral, third, or fourth ventricles. Plugging of the cerebral aqueduct with cold cream fails to prevent grooming in response to lateral ventricle injection of ACTH. However, cold cream plugs in the third ventricle can prevent the subsequent induction of grooming behavior by lateral ventricle injection of ACTH, but only when the plugs are located in the anterior ventral third ventricle in the region of the organum vasculosum laminae terminalis (OVLT) and median eminence. These data suggest the anterior ventral third ventricle as the periventricular site of action of ACTH in eliciting excessive grooming, although it is possible that peptides taken up in this area are transported to other regions to elicit the behavioral response.     

Limbic-midbrain lesions and ACTH-induced excessive grooming.

The induction of excessive grooming by intraventricular administration of ACTH_1–24 was studied in rats with lesions in midbrain-limbic structures. Such areas have been reported to be implicated in mediating ACTH-induced effects on avoidance behavior, sexual excitement or stretching and yawning. Electrolytic lesions in the septal complex, the anterior hypothalamic/preoptic area, the mammillary bodies, the amygdala, the posterior thalamus and dorsal or ventral hippocampus did not interfere with ACTH-induced excessive grooming. Lesioning of the hippocampal complex by aspiration led to an inhibition of excessive grooming depending on the degree of hippocampal damage. Amygdala and hippocampal lesions enhanced the display of stretching and yawning activity after treatment with the peptide. The data indicate differences in the neural substrates mediating the effect of ACTH on extinction of conditioned avoidance behavior, excessive grooming, sexual excitement and stretching and yawning.     

The induction of excessive grooming in the rat by intraventricular application of peptides derived from ACTH: structure-activity studies.

Intraventricular administration of synthetic ACTH-like peptides in the rat induces excessive grooming, stretching and yawning. The present study demonstrates that induction of excessive grooming is dose-dependent and independent of the endocrine system. Structure-activity studies show that ACTH_1–24, ACTH_1–16-NH₂, ACTH_1–16, α-MSH and β_p-MSH are equipotent. Although the presence of the sequence ACTH_5–10 in the peptides studies seems of importance in the induction of excessive grooming, it appeared that C-terminal elongation is necessary for the expression of the activity. Administration of [D-Phe⁷] ACTH_4–10 and [D-Phe⁷] ACTH_1–10 results in appreciable grooming activity of the rat. However, substitution of a D-arginine at the 8 position did not alter the activity of ACTH_4–10. The structure-activity relationship of these peptides on grooming activity of the rat is compared to that known for retardation of avoidance extinction. Although some similarities exist, it is concluded that the expression of excessive grooming and retardation of avoidance activity is mediated through different mechanisms.     

Some characteristics of TRH-induced grooming behavior in rats

Intracerebroventricular administration of TRH induces excessive grooming behavior that is characterized by an important contribution of the elements scratching and paw licking. As compared with other grooming inducing peptides, the pattern of TRH-induced grooming resembles that induced by beta-endorphin rather than those elicited by ACTH or bombesin. TRH-induced excessive grooming is suppressed by pretreatment with haloperidol, naloxone or neurotensin. Haloperidol suppresses TRH-induced grooming in a general way, whereas the suppressive effect of the other drugs is mainly due to a selective reduction of TRH-induced excessive scratching. Combined treatments of rats with TRH and a submaximal dose of ACTH, bombesin or beta-endorphin do not result in higher grooming scores than with single peptide treatment. Excessive grooming elicited by water immersion is not affected by TRH. It is concluded that TRH is undoubtedly an excessive grooming inducing peptide. In situations where excessive grooming is elicited by other peptides or by water immersion, TRH does not further activate the operating systems involved in the existing excessive grooming.     

The effects of neurotensin, naloxone and haloperidol on elements of excessive grooming behavior induced by bombesin

The influence of naloxone, haloperidol and neurotensin was investigated on bombesin-induced excessive grooming in rats. All three drugs reduced the amount of bombesin-induced grooming. Haloperidol induced a general reduction in excessive grooming as induced by bombesin, without changing the composition of grooming behavior, whereas naloxone and neurotensin suppressed bombesin-induced grooming and caused a shift in the distribution of grooming elements. The main suppressive effect of these latter drugs appeared to be on the element scratching. From these data it is suggested that bombesin-induced scratching is mainly displayed by activation of opiate receptor systems, whereas the other elements of bombesin-induced excessive grooming are mainly regulated by dopaminergic systems.     

CRF-induced excessive grooming behavior in rats and mice

We studied the grooming response to lateral ventricle injection of CRF in both rats and mice under similar conditions. One microgram of CRF ICV induced a pronounced increase (3- to 4-fold) in the frequency of self-grooming in rats, but only a much smaller (less than 20%) increase in mice. The minimum effective dose of CRF in rats was 300 ng. Although ACTH1-24 induced less grooming in mice than in rats, the difference in potency did not appear to be sufficient to explain the differences between the effectiveness of CRF in the two species. Whereas ACTH increased all types of grooming scored. CRF increased all forms of grooming except flank scratching with the hind limb. The major effect of CRF was to increase the number of episodes of grooming, whereas ACTH1-24 tended to prolong the length of individual episodes. The excessive grooming induced by ICV CRF was not affected by prior treatment with dexamethasone, suggesting that the increased grooming was not due to secondary release of ACTH from the pituitary. Nevertheless, ICV CRF might induce grooming by releasing MSH/ACTH from cerebral storage sites. CRF-induced grooming, like ACTH-induced grooming, was inhibited by naloxone pretreatment. Despite the small qualitative differences, CRF-induced grooming could be due to secondary release of ACTH.     

Peptide-induced excessive grooming in the rat: The role of opiate receptors

We have investigated the possibility that opiate peptides induce excessive grooming behavior in the rat via a direct action on an opiate receptor by comparing the opiate agonist dynorphin(1–13) with its non-opioid fragment des-tyrosine¹-dynorphin(1–13) (dT-Dyn). We have shown that both peptides are capable of inducing grooming and that this behavior can be suppressed by pretreatment with naloxone. Analysis of the grooming pattern revealed that the response induced by dT-Dyn is qualitatively similar to that induced by ACTH(1–24) and dynorphin(1–13). Cross-tolerance was demonstrated among the various peptides. We conclude that peptide-opiate receptor interaction is not the primary event in the induction of grooming and that the opiate receptor(s) involved are located at another site underlying peptide-induced grooming.     

Dopamine depletion in nucleus accumbens reduces ACTH1–24-induced excessive grooming

Animals were pretreated with 6-OHDA or ascorbate vehicle injected into the nucleus accumbens and tested 10 days later for excessive grooming induced by intracerebroventricular injection of ACTH_1–24. The animals pretreated with 6-OHDA showed a significant decrease in excessive grooming produced by the neuropeptide and this reduction was seen only in the last 30 minutes of a 60-min test session. The results suggest an interaction of ACTH with dopamine systems on the onset and maintenance of excessive grooming.     

Behavioral and neurochemical effects of the new opioid peptide dynorphin--(1-13): comparison with other neuropeptides

This study was undertaken to determine whether the recently discovered opioid-like peptide dynorphin-(1–13) could influence both excessive grooming in the rat and also the activity of the ACTH-sensitive B-50 protein kinase in vitro. Dynorphin-(1–13), when injected intracerebroventricularly at a dose of 1 to 10 μg, resulted in excessive grooming behavior similar to that observed after administration of ACTH-(1–24). In contrast, leu-enkephalin was not effective in the same dose-range. The grooming behavior elicited by both ACTH-(1–24) and dynorphin-(1–13) was blocked by pre-treatment of the rats with naloxone. Furthermore we observed that dynorphin-(1–13) and ACTH-(1–24) were potent inhibitors of B-50 protein kinase. Leu-enkephalin was not effective whereas β-endorphin was a relatively weak inhibitor. Naloxone did not block these in vitro effects. The relationship of these ohenomena to the opioid receptor is discussed.     

The colliculus superior modulates ACTH-induced excessive grooming

In previous studies the involvement of nigrostriatal dopaminergic activity in ACTH(1-24)-induced grooming has been established. It was suggested that the dopaminergic modulation of ACTH(1-24)-induced excessive grooming is exerted through the striato-nigro-collicular pathway. To obtain further evidence it was investigated, whether local application of GABAergic agents into the colliculus superior modulates excessive grooming occurring after an intraventricular injection with ACTH(1-24). It appeared that intra-collicular picrotoxin (a GABAergic antagonist) suppressed ACTH-induced grooming, whereas muscimol (a GABAergic agonist) enhanced the grooming response. The picrotoxin-induced R(unning) F(it) B(ehavior), elicited from the colliculus superior was also seen after intraventricular administration of picrotoxin. A detailed comparison of this behavioral response seen after both routes of administration of picrotoxin suggests that intraventricularly injected picrotoxin may well induce the RFB via a direct effect on the colliculus superior. Lesions placed in the colliculus superior completely abolished picrotoxin-induced RFB, exploration and orientation behavior. Yet, these lesions did not reduce excessive grooming suggesting that although this region may be involved in the modulation of ACTH-induced grooming it is not the primary site of peptide action.     

Nonspecific grooming in rats during the solution of an extrapolation task

Grooming behavior in laboratory brown rats was analysed in the course of extrapolation task solving. Cases of task solution (correct and incorrect) were compared with those when animal "refused" to turn round the screen during search of food bait. In latter cases grooming episodes were more numerous, their latency and duration being higher than during former cases. At the same time the latest stages of experiment (when 8-13 trials a day twice a week were presented) were characterized by more frequent grooming occurrence as well as by longer latencies and duration of grooming episodes. When rats were given I trial a day with one week intervals grooming incidence as well as "refusals" occurrence decreased. The possible participation of animal grooming in arranging the defense reactions against excessive and inadequate activity is discussed.     

Social grooming in the common vampire bat,Desmodus rotundus

Grooming patterns among 65 common vampire bats in hollow tree day roosts were studied by behavioural sampling techniques during a 15-month period. Self-grooming occurred more than social grooming in response to ectoparasites since the proportion of time spent self-grooming and the amount of ectoparasite infestation covaried positively among tree roosts while the time spent grooming others was independent of roots and ectoparasite level. Rates of social grooming were not independent of the sex of participants due to infrequent social grooming by adult males. Two variables, the level of relatedness and a measure of roosting association, which previously were shown to predict food sharing by regurgitation, correlated positively with the rate of social grooming. Since social grooming occurred more often than expected before a regurgitation and correlated with regurgitation frequency, it is suggested that this behaviour facilitates identification of food sharing partners by enabling a grooming bat to monitor other animals' potential for giving or receiving blood.     

Comparison of structural requirements of α-MSH and ACTH for inducing excessive grooming and pigment dispersion

α-MSH and ACTH-like peptides are known to play an important role in the adaptation of many vertebrates to a new environment. These peptides induce pigment dispersion in amphibian melanophores through a receptor-mediated mechanism. In this study we compared the structural requirements of these peptides for melanotropic activity on Xenopus laevis melanophores with those for inducing excessive grooming in the rat. With the exception of ACTH_1–24 there is a close resemblance in structure-activity relationships of the fragments and analogs tested in the two bioassays. [Nle⁴,-D-Phe⁷]-α-MSH is extremely active in both assays. Weak agonists such as [Leu⁹]-α-MSH did not possess antagonistic properties either in the melanophore assay or in the excessive grooming test. The data suggest that the mechanism of action of α-MSH-like peptides in rat brain is receptor-mediated like their action on melanophores.     

Alpha-MSH injected into the substantia nigra or intraventricularly alters behavior and the striatal dopaminergic activity

Rats were injected with 1 μg of alpha-melanocyte stimulating hormone (α-MSH) into the third ventricle and locally in the ventral tegmental area and in different regions of the substantia nigra. The modifications produced on grooming behavior and locomotion as well as on the dopamine content of the nucleus accumbens and the caudate putamen, were studied. Both intraventricular peptide administration and microinjections into the ventral tegmental area induced excessive grooming and a significant increase of the locomotor activity. The dopamine content of the nucleus accumbens and caudate putamen was markedly reduced. Injections of the peptide into the substantia nigra pars compacta failed to induce excessive grooming but did provoke a slight increase in locomotor activity and a smaller change in caudate dopamine content than that observed by injections in the ventral tegmental area or in the third ventricle. Dopamine levels in the nucleus accumbens were not changed. Finally, the injections of α-MSH into the lateral substantia nigra did not produce either biochemical or behavioral changes.The results suggests that α-MSH can modify, directly or indirectly, the striatal dopaminergic activity and that the behavioral alterations observed such as excessive grooming, could be mediated by the activation of the dopamine cells from the ventral tegmental area, that in turn may provoke a significative release of dopamine at the caudate putamen nucleus as well as in nucleus accumbens.     

Hoxb8 is required for normal grooming behavior in mice.

Repertoires of grooming behaviors critical to survival are exhibited by most animal species, including humans. Genes that influence this complex behavior are unknown. We report that mice with disruptions of Hoxb8 show, with 100% penetrance, excessive grooming leading to hair removal and lesions. Additionally, these mice excessively groom normal cagemates. We have been unable to detect any skin or PNS abnormalities in Hoxb8 mutants. These observations suggest that the excessive, pathological grooming exhibited by these mice results from CNS abnormalities. Consistent with this interpretation, we demonstrate Hoxb8 expression in regions of the adult mouse CNS previously implicated in the control of grooming. The aberrant behavior observed in Hoxb8 mutants is not unlike that of humans suffering from the OC-spectrum disorder, trichotillomania. Interestingly, Hoxb8 is expressed in regions of the CNS known as the "OCD-circuit."     

A hormonal basis for sex differences in the self-grooming of rats

The self-grooming behavior of prepubescent male and female rats is described. Sex differences were observed in components of grooming addressed to the genitals, but not in other aspects of grooming. A hormonal basis for the sex difference was examined in two experiments. When females were injected with testosterone propionate (TP) on the day of birth, their subsequent grooming was found to be no different from that of control-treated females. However, males and females gonadectomized at weaning and treated daily with TP each performed significantly more genital self-grooming than oil-treated controls. There were no sex differences in gonadectomized, oil-treated rats, and sex differences in response to TP were limited to greater responsiveness of females to a 50-micrograms, but not 200-micrograms, TP dose. These results lead to the conclusion that sex differences in self-grooming can be accounted for primarily by differences in testosterone availability during the peripubertal period.     

Arginine vasopressin does not mediate heat loss in the tail of the rat

It has been reported that hypothermia induced by arginine vasopressin (AVP) is brought about by a coordinated response of reduced thermogenesis in brown adipose tissue (BAT) and increased heat loss through the tail of rats. However, it is well known that AVP is one of the strongest peripheral vasoconstrictors. Whether the AVP-induced hypothermia is associated with an increase in heat loss through the tail is questionable. Therefore, the present study assessed the relationship between the effects of AVP on tail skin temperature and the induced hypothermic response, and to determine if peripheral AVP administration increases heat loss from the tail. Core, BAT and tail skin temperature were monitored by telemetry in male Sprague–Dawley rats before and after intraperitoneal administration of AVP or vasopressin receptor antagonist. We also analyzed simultaneously of the time-course of AVP-induced hypothermic response and its relationship with changes in BAT temperature, and effect of AVP on grooming behavior. The key observations in this study were: (1) rats dosed with AVP induced a decrease in heat production (i.e., a reduction of BAT thermogenesis) and an increase of saliva spreading for evaporative heat loss (i.e., grooming behavior); (2) AVP caused a marked decrease in tail skin temperature and this effect was prevented by the peripheral administration of the vasopressin V1a receptor antagonist, suggesting that exogenous AVP does not increase heat loss in the tail of rats; (3) the vasopressin V1a receptor antagonist could elevate core temperature without affecting tail skin temperature, suggesting that endogenous AVP is involved in suppression of thermogenesis, but not mediates heat loss in the tail of rats. Overall, the present study does not support the conclusion of previous reports that AVP increased tail heat loss in rats, because AVP-induced hypothermia in the rat is accompanied by a decrease in tail skin temperature. The data indicate that exogenous AVP-induced hypothermia attributed to the suppression of thermoregulatory heat production and the increase of saliva spreading for evaporative heat loss.     

Studies on bombesin-induced grooming in rats

The gross behavior induced by centrally administered bombesin in rats was compared to that elicited by ACTH-(1–24) and the somatostatin analog, des AA^{1,2,4,5,12,13}[D-Trp⁸]-somatostatin (ODT8-SS). Bombesin (0.001–1 μg, ICV) caused dose-related excessive scratching which was qualitatively different from that associated with the other two groom-inducing agents. Bombesin-induced grooming was not markedly affected by behaviorally nondepressant doses of haloperidol, morphine, naloxone or neurotensin. Bombesin was active in genetically hypotrichotic (essentially furless) rats; and, again in such animals, even after numbing the area caudal to the shoulders with lidocaine. Tolerance and cross-tolerance studies with bombesin and ODT8-SS indicated that they produce scratching through different mechanisms. Bombesin caused scratching when injected directly into the periaqueductal gray, but not when administered intravenously. Neither hypophysectomy nor adrenalectomy markedly affected bombesin-induced grooming. This behavior appears to be initiated in the central nervous system and is produced independently of the pituitary-adrenal axis.