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.     

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.     

Behavioral alterations induced by substance P, bombesin, and related peptides in mice

Bombesin, substance P and several structurally related peptides cause excessive grooming behavior after intracerebroventricular injection in mice. The present study describes the behavioral characteristics of these effects after acute administration. Substance P caused an elevation of grooming behavior which was short-lasting (less than 15 minutes), while bombesin induced both grooming and scratching behavior with a duration of action of about 2.5 hours. After repeated injections of high doses of either bombesin or a metabolically stable substance P analog, no tolerance-formation to these peptide-induced effects could be observed. Morphine partially antagonized bombesin-induced behaviors at a dose of 7.5 mg/kg subcutaneously while the same dose did not attentuate substance P-induced grooming. These results suggest that the behavioral changes induced by substance P and bombesin are mediated by distinct mechanisms. The lack of tolerance formation, together with the partial antagonism by morphine, suggests that the bombesin-induced behaviors may be related to a stimulation of nociceptive mechanisms.     

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.     

Age and strain differences in some behavioral effects of intracranial substance P

Intracerebroventricular (ICV) injections of substance P (SP) induce a vigorous reciprocal hindlimb scratching (RHS) syndrome, accompanied by extensive grooming behavior. There is a significant (approximately 1000X) difference in responsiveness to SP, as measured by RHS and grooming, in mice as a function of genetic strain (Swiss/Webster, C57 or DBA) and age. There was considerable specificity in the ability of drugs to increase responsiveness in the least responsive type of mouse (aged DBA/2J). Responding in old DBAs was enhanced by high doses of naloxone, suggesting the involvement of opioid peptides. Significant enhancement of responding by alpha-methyl tyrosine and propranolol, but not by phenoxybenzamine or haloperidol, indicated that beta-adrenergic systems are also involved. Similar manipulations of serotonergic systems were without effect.     

Neuropeptides and thermoregulation: the interactions of bombesin, neurotensin, TRH, somatostatin, naloxone and prostaglandins

In this study we have examined the interactions of bombesin (1 microgram ICV), neurotensin (1 microgram ICV), TRH (10 micrograms ICV), somatostatin (10 micrograms ICV), PGE2 (10 micrograms ICV) and naloxone (10 mg/kg SC) on thermoregulation in the rat at room temperature (20 +/- 1 degree C). Given alone, bombesin, neurotensin, somatostatin and naloxone all produced hypothermia (bombesin greater than neurotensin greater than somatostatin congruent to naloxone). PGE2 was hyperthermic, and TRH had no effect. Bombesin and PGE2 neutralized one another's effects. Neurotensin had no effect on PGE2-induced hyperthermia. Naloxone enhanced the hypothermic effect of bombesin and somatostatin enhanced the rate of onset of hypothermia after bombesin. TRH had no effect on bombesin-induced hypothermia. TRH, somatostatin and naloxone had no effect on neurotensin-induced hypothermia. TRH antagonized the hypothermia due to naloxone and somatostatin.     

Physiological Function of Gastrin-Releasing Peptide and Neuromedin B Receptors in Regulating Itch Scratching Behavior in the Spinal Cord of Mice

Pruritus (itch) is a severe side effect associated with the use of drugs as well as hepatic and hematological disorders. Previous studies in rodents suggest that bombesin receptor subtypes i.e. receptors for gastrin-releasing peptide (GRPr) and neuromedin B (NMBr) differentially regulate itch scratching. However, to what degree spinal GRPr and NMBr regulate scratching evoked by intrathecally administered bombesin-related peptides is not known. The first aim of this study was to pharmacologically compare the dose-response curves for scratching induced by intrathecally administered bombesin-related peptides versus morphine, which is known to elicit itch in humans. The second aim was to determine if spinal GRPr and NMBr selectively or generally mediate scratching behavior. Mice received intrathecal injection of bombesin (0.01–0.3 nmol), GRP (0.01–0.3nmol), NMB (0.1–1nmol) or morphine (0.3–3 nmol) and were observed for one hour for scratching activity. Bombesin elicited most profound scratching over one hour followed by GRP and NMB, whereas morphine failed to evoke scratching response indicating the insensitivity of mouse models to intrathecal opioid-induced itch. Intrathecal pretreatment with GRPr antagonist RC-3095 (0.03–0.1 nmol) produced a parallel rightward shift in the dose response curve of GRP-induced scratching but not NMB-induced scratching. Similarly, PD168368 (1–3 nmol) only attenuated NMB but not GRP-induced scratching. Individual or co-administration of RC-3095 and PD168368 failed to alter bombesin-evoked scratching. A higher dose of RC-3095 (0.3 nmol) generally suppressed scratching induced by all three peptides but also compromised motor function in the rotarod test. Together, these data indicate that spinal GRPr and NMBr independently drive itch neurotransmission in mice and may not mediate bombesin-induced scratching. GRPr antagonists at functionally receptor-selective doses only block spinal GRP-elicited scratching but the suppression of scratching at higher doses is confounded by motor impairment.     

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.     

Effects of bombesin on behavior

This report describes the influence of bombesin on the gross behavior of goldfish, frogs, mice, rats, guinea pigs, rabbits, chicks, pigeons and monkeys. Goldfish, frogs, chicks and pigeons were overtly unaffected by bombesin given centrally and/or peripherally. Mice, rats, guinea pigs, rabbits and monkeys responded quickly to intracerebroventricular (i.c.v.) and/or intrathecal (i.th.) administration of bombesin by displaying a range of behaviors suggestive of altered skin sensation. In mice, bombesin was essentially equipotent as a scratch inducer by i.c.v. and i.th. routes (A50 = 0.010-0.019 microgram) but 6800 times less potent i.p. In rats, bombesin-induced grooming and scratching behaviors were shown to be qualitatively different from those associated with ACTH-(1-24) and thyrotropin releasing hormone. Spantide and [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P (both at 0.20, 0.50 and 0.80 microgram i.c.v.), two proposed bombesin receptor antagonists, did not markedly influence bombesin-induced scratching or hypothermia in rats.     

Comparison between excessive grooming induced by bombesin or by ACTH: the differential elements of grooming and development of tolerance

Bombesin and ACTH-(1-24) induce a dose dependent increase in grooming behavior. Lower doses of bombesin induce a more general type of compulsive grooming in which most elements are involved, whereas higher amounts of bombesin induce a shift towards the element scratching at the cost of bodily grooming and sexual grooming. In contrast ACTH-(1-24) induces a dose dependent increase of all elements of grooming. It is concluded that the grooming displayed by animals treated with ACTH-(1-24) or with bombesin is of a completely different nature. In addition it is observed that under the conditions used tolerance occurs for the grooming inducing effect of ACTH-(1-24), but not for that of bombesin. Moreover, it appears that no cross tolerance exists between bombesin and ACTH-(1-24).     

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.     

Neurotransmitter-mediated open-field behavioral action of CGRP

The effects of central administration of calcitonin gene-related peptide (CGRP) on open-field activity were examined in male rats. Three doses (250 ng, 500 ng and 1 microg) of CGRP given intracerebroventricularly (i.c.v.) were tested on the ambulatory, rearing and grooming activities of the animals. One microg of peptide significantly decreased the ambulatory activity and increased the rearing and grooming activities 30 min after the treatment. The animals were pretreated with different receptor antagonists in doses which by itself did not affect the behavioural paradigm. The decrease in ambulation induced by CGRP was antagonized by acetylcholine-, opioid-, 5HT-receptor and beta-adrenoceptor antagonists. CGRP induced increase in rearing activity was blocked by naloxone, phenoxybenzamine and propranolol. The CGRP-induced increase in grooming behavior was prevented by atropine, haloperidol, naloxone, methysergide and propranolol. The results suggest that different neurotransmitter systems are involved in the action of CGRP on open-field behavior in rats.     

Grooming and Anxiety in Barbary Macaques

Grooming is a fundamental component of sociality in many gregarious animal species, and elucidating the costs and benefits of this behaviour is crucial for understanding its function. There is evidence that animals giving grooming pay a cost in terms of the time and energy they invest, while recipients benefit not just from the removal of dirt and parasites, but also from the relaxing effects of being groomed. Recently, however, studies of primates have indicated that giving grooming may also provide such hedonic benefits, reducing levels of stress or anxiety in the groomer. In this study of free‐ranging adult female Barbary macaques at Trentham Monkey Forest (Stoke‐on‐Trent, UK), we tested the hypothesis that grooming reduces anxiety in the donor and/or the recipient. During focal follows, we quantified females' rates of self‐scratching as a behavioural index of their anxiety levels. Self‐scratching rates in the 2‐min periods after bouts of grooming (given, received and reciprocated) were compared to overall mean self‐scratching rates; we predicted that if grooming reduces anxiety, self‐scratching rates would be significantly lower after grooming bouts than mean levels. We first analysed all grooming bouts and then analysed separately grooming bouts with adult males, with all adult females, with subordinate adult females and with dominant adult females. Contrary to our prediction, self‐scratching rates were never seen to be lower after grooming than mean levels. In fact, for the majority of grooming partner–direction combinations, we found significantly higher rates of self‐scratching after grooming compared to mean levels. The hypothesis that grooming reduces anxiety was therefore not supported. Grooming seems in some cases to increase, not alleviate, anxiety. We explore possible explanations for these unexpected results.     

Effects of adrenergic blockers on corticotropin-releasing factor-induced behavioral changes in rats

The effects of adrenoreceptor blocking agents on corticotropin-releasing factor (CRF)-induced behavioral changes in rats were examined. The i.c.v. injection of 1 micrograms ovine CRF significantly increased the grooming frequency, number of occurrences of rearing and total distance moved. I.c.v. administered phentolamine at a dose of 10 nmol completely suppressed the increase in rearing and total distance moved induced by CRF without affecting the grooming frequency, whereas 100 nmol phentolamine significantly decreased the grooming frequency as well as the rearing and total distance moved. In contrast, propranolol reduced the increase in rearing induced by CRF only at a dose which induced ataxia in rats. The increases in rearing and total distance moved induced by CRF were reduced by 10 nmol of yohimbine and 100 nmol of prazosin. S.c. injection of caffeine (10 mg/kg) produced a significant increase in grooming frequency, rearing, and total movement. Administration of 10 nmol phentolamine and yohimbine did not affect these behavioral changes induced by caffeine, while 100 nmol prazosin suppressed them. Therefore, prazosin depressed the behavior of rats non-specifically. These results suggest that CRF-induced behavioral hyperactivity is mediated at least in part by alpha-noradrenergic, mainly alpha 2-noradrenergic, systems in the brain.     

Corticotropin-releasing factor (CRF) induced anorexia is not influenced by a melanocortin 4 receptor blockage.

CRF and melanocortin (MSH/ACTH) peptides share a number of central effects including anorexia and grooming. The effects of CRF may be secondary, due to CRF's effects on melanocortin peptide release. We investigated if the newly discovered selective melanocortin 4 receptor antagonist HS014 could influence CRF induced anorexia and grooming. The data show that ICV administration of CRF (3 mg/rat), significantly reduced food intake, feeding time and feeding episodes whereas it increased grooming time and grooming episodes. HS014 (5 mg/rat), that previously has been shown to antagonize the anorectic effect and the excessive grooming induced by alpha-MSH, did however not influence any of the behavioral effects induced by CRF when the peptides were administered together. The data indicate that the anorectic and grooming effects of CRF are independent of pathways involving the MC4 receptors. These data suggest that the anorectic and grooming effect of CRF are not due to a secondary effect caused by increase in release of melanocortins acting on the central MC receptors.     

Dynorphin-(1–13) induces spontaneous feeding in rats

Dynorphin-(1–13), a recently isolated opioid peptide stimulates food ingestion in rats after intracerebroventricular administration at doses of 1 and 10 μg. The latency until food ingestion is 22.4 ± 1.9 min. The ability of dynorphin-(1–13) to initiate food ingestion is antagonized by the opiate antagonist, naloxone. The food ingestion is accompanied by excessive grooming behavior.     

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.     

Differences in the pharmacological actions of intrathecally administered neurotensin and morphine

Neurotensin or morphine can each cause hypothermia and an antinocisponsive effect when administered into the liquor spaces of the rat brain. These actions of neurotensin are not blocked by naloxone whereas those of morphine are. The present experiments were carried out to examine the action of each substance following its injection into the subarachnoid space of the spinal cord. Given intrathecally, neurotensin evoked a dose-related fall in the rectal temperature of the rat without exerting an antinocisponsive action. Morphine on the other hand evoked hyperthermia and a dose-related antinocisponsive action. Since neurotensin exerted an effect on rectal temperature opposite to that of morphine and failed to exert an antinocisponsive effect, the data provide further evidence to suggest that neurotensin and morphine exert their effect via different mechanisms. Furthermore, the results also suggest that neurotensin exerts its antinocisponsive action via a supraspinal site.     

Scratching around mating: factors affecting anxiety in wild Lemur catta

Scratching has been successfully used to detect anxiety, a proxy for stress, in primates, from strepsirrhines to Homo sapiens. Here, we investigated the fluctuation of scratching in Lemur catta during the mating season. In particular we evaluated whether scratching (1) varied according to sex and rank differences, (2) increased in the period of maximum stress (around the mating days), and (3) was reduced by grooming. At Berenty (South Madagascar), we followed two lemur groups (23 adult/subadult individuals) and gathered data on self-scratching, aggression, and grooming. Based on perineal area features, we recognized two periods: low swelling (LS), with no estrus female, and high swelling (HS), when at least one female was in estrus. We predicted that aggressive behaviors and anxiety-related scratching would covary. Indeed, scratching peaked in HS, when aggression was also highest. In agreement with previous literature, this result suggests that conflicts around estrus days may raise anxiety levels in the social group. We expected scratching levels to be highest in males because they aggressively compete for females and are subject to mate choice and repeated attacks by dominant females. Instead, the scratching rates were similar in males and females, probably because the high competition, which involves both sexes, dampened intersexual differences. In contrast to our prediction, scratching was not rank dependent, probably because animal ranking positions changed from LS to HS. Finally, we showed that, in ring-tailed lemurs, as well as in other primates, scratching decreases after reciprocal grooming in both periods. This finding provides the first evidence that grooming could assist in reducing anxiety in strepsirrhines.