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Grooming in the mouse is stimulated by the dopamine D1 agonist SKF 38393 and by low doses of the D1 antagonist SCH 23390, but is inhibited by dopamine D2 agonists, D2 antagonists and high doses of SCH 23390.

The effects of manipulating dopamine D1 and D2 receptors on grooming was studied in the mouse. SKF 38393 (D1 agonist) and low doses of SCH 23390 (D1 antagonist) promoted grooming activity. SCH 23390 in neuroleptic doses, RU 24213 (D2 agonist), apomorphine and amphetamine (mixed D1/D2 agonists) and haloperidol (D2 antagonist) all suppressed the tendency of normal mice to groom, though probably by different mechanisms. Duration and frequency of grooming could be influenced differentially by these drugs. The findings suggest opposing roles for dopamine D1 and D2 receptors in the expression of grooming in the mouse.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

On the ontogenetic and sequential characteristics of bombesin-induced grooming in the infant rat.

This paper examined the grooming effects of central injections of the tetradecapeptide bombesin (BN) in the infant rat. Anaesthetized rat pups of 1-20 days of age (n = 7/dose/age) were injected intracerebroventricularly (i.c.v.) with either BN (0.01-1.0 micrograms) or saline (control condition) and placed in heated test cages. Following recovery from the anaesthetic, the subsequent behaviour displayed by the pups was videotaped for the next 60 min. These videotaped responses were then scored for a variety of grooming and other behaviours. Pups of all ages (1-20 days) groomed in response to BN with the 1-day-old pups the least and 20-day-olds the most sensitive to BN. In the 10-day-olds, scratching, in an immature, non-contact form, was elicited by BN. This was replaced by mature, contact type scratching in the sequence of grooming behaviour at 20 days of age. Scratching activities appeared to form a subsystem connected to but nonetheless separate from washing behaviours and this was particularly distinguishable at 20 days of age. Changes in BN-induced grooming appeared to reflect the maturation of the motor capabilities of the developing rat. In conclusion, these results indicate that BN binding sites in the developing rat central nervous system (CNS) are pharmacologically functional from an early stage in ontogeny when there is little or no measurable amount of the peptide itself present in the CNS.

Aging↗

Dopamine denervation of frontal cortex or nucleus accumbens does not affect ACTH-induced grooming behaviour.

Studies with dopamine (DA) receptor antagonists have implicated brain DA systems in the increased grooming behaviour elicited by intracerebroventricular (i.c.v.) administration of ACTH or exposure to a novel environment. To evaluate the potential contributions of DA terminals innervating frontal cortex and nucleus accumbens, stereotaxically guided injections of 6-hydroxydopamine (6-OHDA) were made into these regions of rat brain following peripheral administration of desmethylimipramine and pargyline. Despite an 88% mean reduction of DA, and 68% mean reduction of noradrenaline in frontal cortex, the amount of grooming behaviour observed either in a novel cage, or after i.c.v. injection of ACTH1-24 was not detectably altered. The lesions also did not affect locomotor activity measured during the scoring of grooming, in an open field, in photocell cages, or in a running wheel, even in the animals most severely depleted of DA. Following nucleus accumbens 6-OHDA infusions, depletions of DA as great as 99% were obtained. Animals with accumbens depletions greater than 90% showed the expected attenuation of amphetamine-stimulated locomotor activity. Nevertheless, they exhibited normal grooming scores in a novel cage, and in response to i.c.v. ACTH1-24. It is concluded that dopaminergic terminals in nucleus accumbens and probably those in frontal cortex are not necessary for the expression of novelty- or ACTH-induced grooming.

Adrenocorticotropic Hormone↗

The periaqueductal gray: a prerequisite for ACTH-induced excessive grooming.

The periaqueductal gray is known to be involved in the expression of a variety of behaviours such as aggression, beta-endorphin-induced immobility and peptide-induced excessive grooming. In order to establish whether the periaqueductal gray (PAG) is indispensible for peptide-induced excessive grooming, lesions were placed in the dorsal part of this structure. Subsequently, the grooming-inducing abilities of adrenocorticotropin (ACTH), beta-endorphin and bombesin were tested. The lesioned animals did not display excessive grooming after intracerebroventricular injection of ACTH. beta-Endorphin administration into the lesioned animals resulted in an extreme display of immobility. Local injection of bombesin into the PAG resulted in reduced scratching behaviour followed by immobility. It was hypothesized that excessive grooming (elicited by ACTH) may be mediated through a non-opioid primary target site-situated in the lesioned region of the PAG-while excessive scratching and immobility (elicited by bombesin or beta-endorphin, respectively) may be mediated through an opioid primary target site (situated in the remaining part of the PAG). Furthermore, the analysis of social behaviour of lesioned animals revealed that these animals reacted towards an unfamiliar partner predominantly with freezing behaviour. The increase of beta-endorphin-induced immobility and socially induced freezing (which is morphologically very similar to beta-endorphin-induced immobility) in lesioned animals supports the hypothesis that the release of opioid peptides such as beta-endorphin in the PAG plays a role in the regulation of social behaviour.

Adrenocorticotropic Hormone↗

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.

Adrenocorticotropic Hormone↗

Specific neuroanatomical and neurochemical correlates of grooming and satiety effects of bombesin.

Experiments characterized the behavioral effects of bombesin (BN) administered systemically (1-8 micrograms/kg; IP) or centrally at the nucleus tractus solitarius (NTS) and the nucleus accumbens (NA) (0.0001-1.0 microgram/0.5 microliter). The role of dopaminergic system(s) in the mediation of BN-induced behavioral effects in rats was also investigated. In the "satiety" paradigm, grooming and eating behaviors were monitored in 5-hr-food-deprived rats trained to take a portion of their daily food intake over the 20 min observation period. The elicitation of grooming and satiety appeared to be specific to BN administration at the NTS but not the NA. The dopaminergic system(s) did not appear to mediate the behavior effects of BN intra NTS. The BN-induced grooming profile appeared to be paradigm independent although the baseline grooming profile was not. At the NTS, a dissociation of BN-induced grooming and satiety was evident on the basis of time-course and dose-effect. The similarity of the time-course of satiety induced by BN injected at the NTS and IP suggested that BN may mediate a physiological satiety signal at the NTS. Furthermore, since BN induced satiety 10(4) more potently and 20% more efficaciously intra NTS than IP, the NTS may be a critical site for the action of BN on satiety.

Animals↗

Stress induced grooming in the rat--an endorphin mediated syndrome.

Exposure of adult male Sprague--Dawley rats to a non-traumatic noise-light stress procedure subsequently increased grooming behavior in a novel environment. The grooming syndrome was marginally facilitated by adrenalectomy and by hypophysectomy. Opiate blockade by naltrexone returned grooming to basal levels. This suggests that stress induced grooming is not dependent upon pituitary-adrenal integrity for its expression, although it may be modulated by the latter. On the other hand this form of grooming may depend upon an endogenous opiate system.

Adrenalectomy↗

Paternal alcohol consumption affects grooming response in rat offspring.

Grooming behavior in response to novelty and water immersion was examined in rat offspring sired by males consuming liquid alcohol diets containing 35%, 17.5% or 0% ethanol-derived calories (EDC). In the first study, offspring were tested at 35-38 days of age under conditions of lights on or off. Offspring in the 35% EDC group groomed less than controls. Lighting conditions did not affect grooming significantly. In the second study, animals were immersed in a water bath for 15 seconds and were then placed in the same observation chambers. As in the previous study, animals sired by alcohol-consuming fathers groomed considerably less than controls. These results were interpreted as suggesting offspring sired by alcohol-consuming fathers have a blunted response to conditions which spontaneously elicit behavior like grooming or ambulation.

Animals↗

The effects of CCK-4 on dopamine D1 agonist-induced grooming are blocked by a CCK(A) receptor antagonist: evidence for a novel CCK receptor subtype?

The neuropeptide cholecystokinin (CCK) has been shown to interact with dopamine in various ways, including attenuation of dopamine D1 receptor-mediated vacuous chewing and grooming. While we have demonstrated a clear role for the CCK(A) receptor in the attenuation of dopamine D1 agonist-induced vacuous chewing, studies of grooming yielded anomalous results. We examined the effects of selective CCK receptor antagonists on the attenuation of SKF 38393-induced grooming by the CCKB agonist CCK-4. Administration of SKF 38393 (5 mg/kg s.c.) to male Sprague-Dawley rats resulted in a significant increase in grooming which was reduced to control levels by CCK-4 (20 mg/kg i.p.). Pretreatment with either the CCKA receptor antagonist devazepide or the CCK(B) receptor antagonist L-365,260 significantly attenuated this effect over a range of doses (20, 100, 500 microg/kg i.p.). The suppression of dopamine D1 agonist-induced grooming by CCK-4 does not appear to reflect a non-specific effect of anxiogenesis, as it was unaffected by the anxiolytic diazepam. The CCK receptor antagonists alone were without behavioural effect. Taken together with previous studies in models of anxiety and analgesia, our findings lend further support to the hypothesis that CCK-4 may act at a novel receptor subtype.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

m-CPP-induced self-grooming is mediated by 5-HT2C receptors.

m-Chlorophenylpiperazine (m-CPP), a potent 5-HT receptor agonist, is known to induce self-grooming in rats and exacerbate symptoms in patients with obsessive-compulsive disorder (OCD). To characterise the possible role, 5-HT(2B) and 5-HT(2C) receptors play in m-CPP-induced self-grooming, subtype-selective receptor antagonists were used. m-CPP significantly increased the amount of self-grooming in male Sprague-Dawley rats. This effect followed a bell-shaped dose-response curve with a peak at 0.6 mg/kg, i.p. Pretreatment with SB-242084, a subtype-selective 5-HT(2C) receptor antagonist (0.1-0.5 mg/kg, i.p.), reversed m-CPP-induced self-grooming. In contrast, pretreatment with the subtype-selective 5-HT(2B) receptor antagonist SB-215505 (1 mg/kg, i.p) did not block the effect of m-CPP. Two days after depletion of brain 5-HT by p-chlorophenylalanine (p-CPA, 2 x 50, 2 x 100 mg/kg, i.p.) m-CPP-induced responses were significantly enhanced compared to controls. Our studies provide evidence that direct activation of 5-HT(2C) receptors mediate m-CPP-induced self-grooming and the depletion of brain 5-HT sensitizes these receptors.

Aminopyridines↗

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."

Aging↗

Correlation of increased grooming behavior and motor activity with alterations in nigrostriatal and mesolimbic catecholamines after alpha-melanotropin and neuropeptide glutamine-isoleucine injection in the rat ventral tegmental area.

1. We wished to further study the behavioral effects of alpha-melanotropin (alpha-MSH), melanin-concentrating hormone (MCH), and neuropeptide glutamine-isoleucine (NEI). 2. To this effect we administered alpha-MSH, MCH, and NEI in the ventral tegmental area of the rat, a structure where these neuropeptides are highly concentrated. To further elucidate the biochemical mechanisms of the behavioral effect of these neuropeptides, we determined the degree of grooming behavior and the levels of catecholamines. after neuropeptide administration. 3. We preselected those animals responding to the central injection of alpha-MSH with excessive grooming behavior. We administered the neuropeptides at the dose of 1 microg/0.5 microL, in each side of the ventral tegmental area, bilaterally. We studied grooming behavior, locomotor activity, and total behavior scores, 30 and 65 min after administration of the peptides. 4. Three groups of animals were decapitated immediately after the injection of the neuropeptides, and 30 or 65 min after injection. We measured dopamine (DA), noradrenaline (NA), and the dopac/dopamine ratio (DOPAC/DA) to determine steady state levels of catecholamines and an indirect measure of DA release and metabolism, respectively. 5. Injections of alpha-MSH produced significant elevations in grooming behavior, locomotor activity, and total behavior scores, both 30 and 65 min after peptide administration. This was correlated with significant decreases in DA content, increases in DOPAC content, and increases in the DOPAC/DA ratio. In the caudate putamen, changes in catecholamines occurred both at 30 and 65 min after injection. In the nucleus accumbens, changes were present at 65 min after injection. Conversely, there were no alterations in NA content, either in the caudate putamen or in the nucleus accumbens, at any time after the injection. 6. Injections of NEI resulted in significant elevations in grooming behavior, locomotor activity, and total behavior scores, both 30 and 65 min after peptide administration. This was correlated with increased DOPAC/DA ratio in the nucleus caudatus but not in the nucleus accumbens. Conversely, NEI produced increased NA concentrations in the nucleus accumbens, but not in the nucleus caudatus. 7. Injections of MCH did not produce significant changes in behavior or significant changes in nucleus caudatus or nucleus accumbens catecholamines. 8. Our results indicate (a) There is a correlation with alterations in behavior as induced for the neuropeptides injected here, and changes in extrapyramidal catecholamines. (b) There is a correlation between alterations in behavior and increases in DOPAC/DA ratio in the nucleus caudatus. (c) There is a correlation between alterations in behavior and alterations in catecholamines in the nucleus accumbens. In the nucleus accumbens, DOPAC/DA ratio is changed after alpha-MSH, and NA ratio is changed after NEI injection. (d) Absence of alterations in extrapyramidal catecholamines, and in particular in catecholamines in the nucleus accumbens, correlates with absence of behavioral alterations after neuropeptide administration to the ventral tegmental area. 9. In conclusion, the behavioral effect of exogenous administration of neuropeptides in the ventral tegmental area is peptide-specific, and is probably associated with alterations in catecholamine metabolism and release in the nucleus caudatus and the nucleus accumbens. Both alpha-MSH and NEI seem to stimulate the nigrostriatal DA system. While alpha-MSH appears to stimulate the mesolimbic DA system as well, NEI may exert its actions not through the DA, but through the NA mesolimbic system. The precise contribution of DA and NA, and the relative role of the nucleus caudatus and nucleus accumbens in these behaviors remain to be elucidated.

Animals↗

Effect of serotonergic and catecholaminergic antagonists on mild-stress-induced excessive grooming in the rat.

Excessive grooming was induced in male rats by two ip injections of physiological saline. This mild stressful procedure did not modify open-field locomotion in 5-min trials. Methysergide (15 mg/kg) and pizotifene (5 mg/kg), serotonergic blockers, selectively prevented the grooming response to saline without affecting locomotion. Haloperidol (.4 mg/kg) also prevented the excessive grooming. However, this dopaminergic blocker impaired locomotion. The alpha- or beta-adrenoceptor antagonists phentolamine (20 mg/kg) and l-propranolol (20 mg/kg) did not prevent the excessive grooming in response to saline and did not affect locomotion. The results suggest that some serotonergic pathways in the brain are involved in the grooming response to a mild stress and support previous findings on the role of dopaminergic systems on this activity.

Animals↗

Serotonin, the superior colliculus, and grooming behavior in cats with neocortical lesions.

Previous studies of cats with pontile lesions indicate that a serotonergic deficit exists in the superior colliculi and that this deficit is involved in the genesis of an abnormal grooming behavior. Cats with frontal neocortical lesions exhibit the same serotonergic deficit and the same abnormal grooming behavior. The present study established that the serotonergic deficit is involved in the mediation of the abnormal grooming behavior in cats with frontal neocortical lesions. Microinjections of 5-hydroxytryptophan (5-HTP) and 5-hydroxytryptamine (5-HT) into the superior colliculi abolished or signigicantly reduced the abnormal behavior in cats with frontal neocortical lesions, whereas no effects of 5-HTP were observed after injections into the cerebrospinal fluid above the superior colliculi, into the tegmentum beneath the superior colliculi, or into the medial dorsal nucleus rostral to the superior colliculi. Other substances (tryptophan, noradrenaline, and gamma-amino-butyric acid) had no effect on the abnormal behavior when injected into the superior colliculi. Further evidence implicating a serotonergic deficit in the mediation of the abnormal behavior was obtained by systemic injections: The abnormal behavior was abolished with 5-HTP in cats with frontal neocortical lesions and in adrenalectomized cats that were previously treated with p-chlorophenylalanine.. The present study also demonstrated that the abnormal grooming behavior is induced by frontal neocortical lesions and not by more caudal lesions of the neocortex. The anatomical relations between the frontal neocortex and the superior colliculus and the role of these structures in grooming behavior are discussed.

5-Hydroxytryptophan↗

Role of glucocorticoids in an abnormal grooming behavior in cats with pontile or frontal neocortical lesions.

Cats with pontile or frontal neocortical lesions display a tactually elicited dissociation of appetitive and consummatory grooming behaviors. Systemic administration of glucocorticoids abolished the abnormal grooming behavior in cats with lesions, even when the stimulatory effect of glucocorticoids on serotonin metabolism was blocked by administration of p-chlorophenylalanine (PCPA). Microinjections of glucocorticoids into the superior colliculi also significantly decreased the abnormal grooming behavior. Adrenalectomized cats did not display the abnormal grooming behavior, but the abnormal behavior did occur in PCPA-treated adrenalectomized cats. Administration of either glucorticoids or 5-hydroxytryptophan abolished the abnormal behavior in PCPA-treated adrenalectomized cats. Thus, it appears that the pontile and frontal neocortical lesions produce deficits in both glucocorticoids and serotonin, and these deficits are necessary and sufficient conditions for inducing the abnormal grooming behavior.

11-Hydroxycorticosteroids↗

Raphe lesions and 5,7-dihydroxytryptamine induce grooming reflexes in adrenalectomized cats.

Grooming reflexes are induced by frontal neocortical, pontile, or spinal lesions in dogs and cats. In intact cats, the combined treatments of adrenalectomy and para-chlorophenylalanine administration induce grooming reflexes. Two other ways of depleting serotonin (with 5,7-dihydroxytryptamine and raphe lesions) were combined with adrenalectomy in the present study as further tests that serotonin and glucocorticoid hormones are the critical factors in the induction of grooming reflexes. Because the deficit in serotonin is confined to the superior colliculi in cats with frontal and pontile lesions, 5,7-dihydroxytryptamine (5,7-DHT) was injected directly into the superior colliculi at eight sites, 2 microgram/site (1 microliter at .5 microliter/min). Electrolytic dc lesions of the dorsal and superior central raphe nuclei were made in another group, and then both groups were adrenalectomized. There were three control groups: (a) a group with vehicle injections in the superior colliculi and laporatomies, (b) a group with 5,7-DHT injections in the superior colliculi, and (c) a group with the raphe lesions. Large receptive fields for grooming reflexes occurred only in the groups with combined treatments. Thus the mechanism of induction of grooming reflexes by central nervous system lesions involves independent changes in a hormonal and a neurotransmitter system which combine to effect the change in behavior.

5,7-Dihydroxytryptamine↗

Environmental constraints on motor abilities used in grooming, swimming, and eating by decorticate rats.

In a number of successive tests, grooming, swimming, and eating behaviors of decorticate rats were reexamined by evoking the behaviors in various circumstances (stimulus conditions). The rats showed normal-length grooming sequences during spontaneous home cage grooming; when grooming was elicited by removing the rats from their home cage and soaking their fur by a brief swim, grooming-sequence length was abbreviated. In cold (18 degrees C) water, they swam well and with exaggerated vigor and frequently inhibited forelimb movements; in warm (37 degrees C) water, they swam poorly and paddled with all four limbs. To eat small pieces of food, they sat up and used their forepaws as do normal rats, but they frequently dropped the food; they did not use their forepaws to eat large pieces of food. When given powdered food, they first tried to grasp it in their mouth while they scratched at the floor surface with their front limbs; thereafter, they became increasingly proficient in licking it up. Thus, in a narrow range of stimulus conditions, decorticate rats can make movements resembling those of normal rats. They also improve with practice in some (eating powdered food) but not other (forepaw immobility, eating large food pellets) tasks. The study shows that in order to elucidate the role of the cortex in control of motor behavior, it is necessary to obtain "behavior profiles" of each behavior by testing the animals repeatedly and under widely varying test conditions.

Animals↗

Role of thyroid hormones in an abnormal grooming behavior in thyroidectomized cats and cats with pontile lesions.

Thyroidectomized cats and cats with pontile lesions exhibit the same abnormal grooming behavior. Investigations were conducted to determine whether the abnormal grooming behavior in cats with pontile lesions was attributable to a hypothyroid condition. Administration of thyroid hormones abolished the abnormal behavior of thyroidectomized cats but was without effect in cats with pontile lesions. Studies of brain and blood levels of thyroid hormones in cats with pontile lesions failed to detect any differences from normal cats, and normal effects of thyroid hormones on evoked potentials to light flashes and to clicks were obtained in cats with pontile lesions. It was concluded that any thyroid dysfunction that may exist in the cats with pontile lesions was not involved in the genesis of the abnormal grooming behavior. Because the abnormal grooming behavior fluctuates rhythmically during the year, an endocrine hypothesis was entertained as the source of the fluctuations; endocrine concomitants of the abnormal behavior were investigated with longitudinal studies. The urinary excretion of 11-hydroxycorticoids exhibited a significant negative correlation with the abnormal behavior. When compared with that of normal cats, the plasma level of 11-hydroxycorticoids of thyroidectomized cats was significantly decreased. Intramuscular injections of 11-hydroxycorticoids abolished the abnormal behavior in both thyroidectomized cats and cats with pontile lesions. These results considered together with previous findings indicate that thyroidectomy and pontile lesions induce similar changes in 11-hydroxycorticoid and serotonergic functions-changes that are critical features of the physiological bases of the abnormal grooming behavior in both groups.

11-Hydroxycorticosteroids↗