Grooming Response Research Articles

The effects of intracerebroventricularly injected corticotropin-releasing factor (CRF) on the central nervous system: Behavioural and biochemical studies

Intracerebroventricularly (ICV) administered corticotropin-releasing factor (CRF) produces behavioural activation in rats. The present study was designed to investigate the effects of ICV administered CRF on not only locomotor activity, but also the turnover rates of dopamine (DA) and norepinephrine (NE) in various discrete brain regions in rats. ICV administration of 1 μg CRF produced a significant increase in locomotor activity, while ICV administration of 10 μg CRF caused slow stereotypy with prominent grooming. The 3,4-dihydroxyphenylacetic acid/DA ratio, e.g. DA utilization, was increased in the frontal cortex (FC), striatum, hippocampus (HIPP) and amygdala. DA utilization in the FC increased in a dose dependent manner, suggesting that the hyperactivity of the mesocortical DA system is relevant to the grooming response. The 3-methoxy-4-hydroxy-phenylglycol/NE ratio was increased in the FC and HIPP, indicating the involvement of the dorsal NE pathway in ICV CRF-induced behavioural changes in rats. These findings are discussed in connection with the hypothesis that CRF produces behavioural changes consistent with increasing emotionality, especially anxiety, and may serve as a neuroendocrine modulator of stress-enhanced behaviour.

Age-related changes in the motor response to environmental novelty in the rat

To examine age-related changes in responsiveness to environmental novelty, 3-, 12-, and 24-month-old male Fischer 344 rats were maintained on a restricted diet and exposed to a modified open field for 10 min on each of 10 consecutive days. On the first day of testing, animals of all groups showed equal amounts of rearing. While the 3-month animals continued to show approximately the same levels of rearing until the 8th day, by day 5, the older groups (12- and 24-month) had significantly reduced their rearing. Conversely, grooming was initially highest among the 24-month-old animals. While 3- and 12-month rats showed habituation of grooming, the oldest animals failed to habituate their grooming response by day 5. By day 10, there were no significant differences among the groups in either rearing or grooming. Although food was available in the center of the modified open field, there was little eating and there were no differences among groups. However, all animals did eat quickly when food was made available in their home cages. Thus, all animals displayed a profile of stress-related responses to open field exposure. Plasma corticosterone levels likewise were elevated in the modified open field. Some, but not all, components of this response profile habituated over teh 10 dyas of exposure Three-month-old animals responded to the novelty predominantly by rearing and 24-month animals predominately by grooming. This suggests that with aging, locomotor responses to stress are replaced by a more self-directed form of displacement activity.

Excessive grooming induced by the administration of codeine and morphine

Previous studies have shown that peripheral injections of the codeinone RX 336-M can induce excessive grooming in rats in an age-dependent fashion. The present experiment demonstrates that codeine, itself, also induces excessive grooming but with apparent equal effectiveness at all ages tested. Because of the structural similarity between codeine and morphine, the effects of intraperitoneally administered morphine were examined as well. Morphine was found to produce a temporal course of excessive grooming quite different from that produced by codeine. Morphine did not affect grooming in the first half (30 min) of the observation period, but accentuated it, briefly, for the next 30-45 min. Intraventricular administration of codeine at doses of 0.3 or 1.0 microgram/3 microliter had no effect on grooming in animals previously shown to demonstrate excessive grooming in response to either dose.

Changes in behavioural responses to the combined administration of D1 and D2 dopamine agonists in normosensitive and D1 supersensitive rats.

The selective D1 receptor stimulant SKF 38393 dose-dependently increased grooming time in rats without affecting locomotor activity or eliciting stereotyped behaviour. The selective D2 receptor agonist LY 171555 induced a dose-dependent increase in rat motility, a marked decrease in grooming time and a low occurrence of stereotyped behaviour. Concurrent administration of the two selective agonists induced high-degree stereotyped responses and reductions in locomotor and grooming behaviours. Rats withdrawn from repeated treatment with the selective D1 receptor blocker SCH 23390 (0.05 mg/kg twice daily for 21 days; 7 days of washout) did not exhibit any change of locomotor and grooming responses to threshold doses of LY 171555 and SKF 38393 given alone or in combination. On the contrary, a significantly greater occurrence of high-degree stereotyped responses to the combination of the two selective agonists was observed. The data support the view that D1 and D2 receptors have a cooperative role in the generation of stereotypies and suggest that D1 receptor supersensitivity needs D2 stimulation to be revealed.

Excessive grooming in response to opiate drugs. The ontogeny of responsiveness.

Annals of the New York Academy of SciencesVolume 525, Issue 1 p. 321-329 Excessive Grooming in Response to Opiate Drugs The Ontogeny of Responsiveness ROBERT L. ISAACSON, ROBERT L. ISAACSON Center for Neurobehavioral Sciences, Department of Psychology, University Center at Binghamton, Binghamton, New York 13901Search for more papers by this author ROBERT L. ISAACSON, ROBERT L. ISAACSON Center for Neurobehavioral Sciences, Department of Psychology, University Center at Binghamton, Binghamton, New York 13901Search for more papers by this author First published: May 1988 https://doi.org/10.1111/j.1749-6632.1988.tb38616.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume525, Issue1Neural Mechanisms and Biological Significance of Grooming BehaviorMay 1988Pages 321-329 RelatedInformation

Is stimulation of both D1 and D2 receptors necessary for the expression of dopamine-mediated behaviors?

Recent electrophysiological findings have indicated that D1 dopamine (DA) receptor stimulation by SKF 38393 enables the inhibitory effects of the D2 receptor agonist quinpirole on nucleus accumbens neurons. In the present study, a similar interaction was shown for quinpirole-induced stereotyped behaviors. In control rats, SKF 38393 enhanced the stereotyped responses induced by quinpirole, converting lower-level stereotypies (sniffing and rearing) to more intense oral behaviors (licking and gnawing). In rats depleted of DA (79% reduction) by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT), the behavioral effects of quinpirole were abolished. However, quinpirole-induced stereotyped responses were reinstated by SKF 38393 suggesting that D1 receptor stimulation by endogenous DA is necessary for D2 receptor-mediated stereotyped responses (sniffing, rearing). In support of this suggestion, stereotyped behaviors produced by the non-selective D1/D2 agonist apomorphine were not affected by AMPT pretreatment. In contrast to the effects of quinpirole, the ability of SKF 38393 to induce grooming responses was not abolished by AMPT pretreatment or by combined pretreatment with AMPT and reserpine (greater than 99% DA depletion). These results indicate that D1 receptor stimulation enables D2 receptor-mediated stereotyped responses, but that this relationship is not reciprocal since D2 receptor stimulation is not necessary for the grooming response elicited by SKF 38393.

Molecular transduction mechanisms in ACTH-induced grooming.

Intraventricular administration of ACTH1-24 induces excessive grooming in the rat. Ethogram analysis shows that the peptide does not alter grooming behavior seen in a novel box, but that it prolongs the duration of the grooming bout. Extensive structure-activity studies have been performed which suggest that the active site lies in a region (5-13) of the ACTH molecule. Interestingly, the (1-24) sequence is fully active, whereas (1-10) and (11-24) alone or in combination are inactive, pointing to a specific stereoconformation necessary to induce grooming. However, despite the fact that there are ACTH-and/or alpha-MSH-containing peptidergic neurons, no conclusive evidence is available demonstrating stereospecific, saturable binding sites for these peptides in brain. The analysis of the neural substrate underlying ACTH-induced excessive grooming has been performed by means of electrolytic lesions of specific brain regions and by neuropharmacological manipulations. The data suggest that the periaqueductal gray is the primary target for ACTH and that the activity of neostriatum and accumbens, via a nigro-colliculus-periaqueductal gray pathway, modulates the display of excessive grooming. An important feature of the neural substrate is that it displays single-dose tolerance to the peptide during the first hours after the first peptide injection. It is suggested that the tolerance is a feature of an opioid receptor-containing component of the neural substrate. The molecular mechanism of action of ACTH is complex and may involve different transmembrane signal transduction systems. The peptide decreases the degree of phosphorylation of a neuron-specific, synaptic phosphoprotein B-50 by inhibition of protein kinase C. It is concluded that changes in the degree of phosphorylation of B-50 regulate the activity of the lipid kinase phosphatidylinositol 4-phosphate kinase. Therefore, the B-50 protein seems to be part of a negative feedback loop in the receptor-activated hydrolysis of phosphatidylinositol 4,5-bis-phosphate (PIP2). There is increasing evidence that the molecular mechanism by which ACTH brings about the grooming response involves a change in phosphorylation of B-50. Firstly, the structure-activity relationship of ACTH-induced excessive grooming is nearly identical to that obtained for ACTH-induced inhibition of protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)

The spontaneously diabetic wistar-bb rat manifests altered grooming and catalepsy responses: Implications of impaired dopamine function

Qadeer Ahmad and Zulfiquar Merali. The Spontaneously Diabetic Wistar-BB Rat manifests altered grooming and catalepsy responses: implications of impaired dopamine function. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1988, 12 :291–298 1. 1. The purpose of this study was to investigate the hypothesis that the grooming and catalepsy behaviors, believed to be mediated predominantly by the D1 and D2 dopamine receptor based mechanism(s), respectively, are altered in the Spontaneously Diabetic Wistar-BB Rat (SDR). 2. 2. The insulin treated male SDR (5–6 months diabetic) and a genetically matched Non-Diabetic (NDR) control group were monitored for pharmacologically-induced catalepsy as well as stress-induced grooming. 3. 3. Results obtained indicated that the SDR manifested an increased sensitivity to i) the cataleptogenic effects of haloperidol (0.3–1.0 mg/kg; s.c.) and ii) to the grooming response elicited by a mild stressor (novel environment), when compared to the NDR group. However, under more stressful conditions, the NDR groomed as much as the SDR. The altered behavioral sensitivity of the SDR may be a consequence of impaired dopaminergic neurotransmission and the subsequent upregulation of D1 receptors.

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 ACTH 1–24 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 ACTH 1–24 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.

Pharmacological characterization in the rat of grooming and other behavioural responses to the D1 dopamine receptor agonist R-SK&F 38393

Grooming, sniffing, Iocomotor and rearing responses to the D(1) dopamine receptor agonist SK&F 38393, as the racemic compound or its R-enantiomer, were characterized pharmacologically using typical neuroleptics, non-dopaminergic antagonists, selective D(1) antagonists and selective D(2) antagonists. The typical neuroleptics haloperidol and flupenthixol blocked all behaviours induced by SK&F 38393; this action of flupenthixol was stereoselective for its cis(Z)-isomer but not its trans(E)-isomer. Non-dopaminergic antagonists failed to reproduce the consistent effects of typical neuroleptics. The selective D(1) antagonist SCH 23390 potently blocked all responses to SK&F 38393. A related selective D(1) antagonist, SK&F 83566, also blocked these responses, and this action was stereoselective for its R-enantiomer but not its S-enantiomer. These data suggest that D(1) receptor stimulation is the primary mechanism underlaying the induction of these behaviours by SK&F 38393. However, the expression of certain individual responses to SK&F 38393 were sensitive to attenuation by the selective D(2) antagonists sulpiride or metoclopramide. These results extend the emerging view that the D(1) receptor is behaviourally relevant and that there exist functional interactions between D(1) and D(2) receptor systems in the regulation of behaviour.

Altered grooming responses to stress in rats exposed prenatally to ethanol

The effects of prenatal alcohol exposure on grooming, locomotion, and rearing in response to stress were examined in adult rats whose mothers consumed a liquid diet containing 35% ethanol-derived calories (EDC). Offspring of both pair-fed 0% EDC mothers and ad libitum chow-fed mothers were included as controls. In Experiment 1, females groomed more than males following placement into a novel test chamber, but no differences due to prenatal treatment were observed. Ethanol-exposed animals groomed more than controls following the stress of a forced 1-min swim (Experiment 2), but when rats tested in Experiment 1 were observed again after forced swim stress (Experiment 3), no differences due to prenatal treatment or sex were observed. Experiment 4 examined the effects of pretreatment with 1 mg/kg naloxone on novelty-induced grooming and as in Experiment 1 prenatal treatment did not affect grooming responses. Females again groomed significantly more than males and naloxone reduced grooming equally for all groups. The results suggest that novelty-induced grooming is a sex-influenced behavior, with females grooming more than males, and that animals exposed prenatally to alcohol and tested as adults may have altered responses to certain stressors (i.e., forced swim) under specific conditions. The altered grooming response of alcohol-exposed rats to swim stress can be eliminated by preexposing them to novelty stress.

Changes in motor activities induced by microinjections of the selective dopamine agonists LY 171555, quinpirole hydrochloride, and SK&F 38393 into the Habenula nucleus

The effects on behaviour of microinjections into the habenula complex of selective agonists for dopamine D-1 (SK&F 38393) and D-2 (LY 171555) receptors were documented in a holeboard, open-field test. The D-2 agonist reduced grooming responses, locomotor activity and rearing behaviour. In contrast, the D-1 agonist increased rearing and locomotor activity but was without effect on grooming responses. Neither drug produced significant effects on inspective hole exploration. The data extend findings of behavioural importance of intrahabenular receptor activation and provide direct evidence in support of the functional and behavioural importance of intrahabenular dopamine receptor sites. The findings are consistent with suggestions for feedback regulation of habenular efferents to midbrain dopaminergic neurons. Effects of both receptor agonists on some responses but not others indicates potential complex interactions between D-1 and D-2 receptors within the habenula.

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.

Behavioural effects of tachykinins and related peptides

Substance P (SP) and related tachykinins administered either intracerebroventricularly or directly into the ventral tegmental area of the mesencephalon of rat brain caused increased locomotor activity, grooming behaviour and wet dog shakes. Kassinin, eledoisin, neurokinin A and DiMe-C7, agonists with some selectivity for the SP-E-receptor elicited the greatest locomotor activity and wet dog shake responses, whereas SP and physalaemin which are more selective for the SP-P-receptor were most effective in eliciting the grooming response.

The collicus 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 ssuppressed 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.

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.

Dopaminergic modulation of ACTH-induced grooming

ACTH-(1-24)-induced grooming was studied after administration of the peptide into the substantia nigra or intracerebroventricularly (i.c.v.). The modulation of dopamine receptors in neostriatum (with haloperidol and apomorphine) and nucleus accumbens (with 3,4-dihydroxyphenylamino-2-imidazoline hydrochloride; DPI and ergometrine) was investigated. In the nucleus accumbens, the modulatory effects of ergometrine and DPI on ACTH-(1-24)-induced grooming were based on their affinity for dopamine receptors and not on their affinity for adrenoceptors. Intrastriatal application of dopaminergic agents inhibited i.c.v. ACTH-(1-24)-induced excessive grooming, whereas the grooming score was enhanced if ACTH-(1-24) was administered into the substantia nigra. The finding of differential effects of dopaminergic agents on ACTH-induced excessive grooming depending on the route of administration indicate that i.c.v. ACTH-induced excessive grooming is not mediated solely through the substantia nigra. The increase in grooming behavior seen after the intrastriatal administration of dopaminergic agents - when ACTH was injected into the substantia nigra - suggests the involvement of the striato-nigral GABAergic pathway. Local injections of ACTH-(1-24) into the periaqueductal gray also induced excessive grooming. Since a second injection of ACTH-(1-24) into the periaqueductal gray did not lead to a grooming response, irrespective of where the first injection of ACTH-(1-24) was given (i.c.v. into the nigra or via the periaqueductal gray) it is suggested that this structure seems to play a primary role in the induction of excessive grooming. Therefore the modulatory effects of the dopaminergic influence on ACTH-(1-24)-induced grooming may be exerted via the striato-nigro-collicular pathway.

Ontogeny of the behavioral effects of lysergic acid diethylamide in cats.

The ontogeny of the behavioral effects of lysergic acid diethylamide (LSD) was examined in cats between the ages of 4 and 112 days postpartum. The kittens showed little LSD-induced behavioral change prior to 14 days of age. By the age of 21 days, however, the kittens exhibited many of the behavioral signs characteristic of LSD-induced behaviors in adult cats. These behaviors include limb-flicking, abortive grooming, head-shakes, grooming, and investigatory responses. In general, these behaviors began at a low frequency of occurrence, then increased rapidly with advancing age, reaching adult values by approximately 35-40 days of age, and remained relatively constant through 112 days postpartum. The time course for the behavioral effects following an acute injection of LSD showed the adult pattern, i.e., persisting for approximately 8 hr post-injection, from their earliest appearance during ontogeny. Young kittens (21-42 days of age) were resistant to the development of tolerance following repeated administration of the drug. LSD was capable of eliciting certain behaviors, such as head-shakes and grooming, well in advance of the age at which they normally appear spontaneously. This indicates that the neuronal and musculature substrata are developed for the performance of these behaviors long before the kitten naturally employs them.

Dopaminergic behaviour stereospecific promoted by the D1 agonist R-SK & F 38393 and selectively blocked by the D1 antagonist SCH 23390.

The selective D1 dopamine receptor agonist R-SK & F 38393 (20 mg/kg), but not its S- antipode , stereospecifically promoted episodes of prominent grooming behaviour. Typical stereotyped behaviour, such at that induced by apomorphine, was not seen. Grooming responses to 20 mg/kg R-SK & F 38393 were blocked by 0.1-0.5 mg/kg of the selective D1 antagonist SCH 23390 but not by 1.0-5.0 mg/kg of the selective D2 antagonist metoclopramide, while stereotyped behaviour induced by 0.5 mg/kg apomorphine was blocked by both antagonists. These results are consistent with certain individual dopaminergic behaviours such as grooming being mediated by D1 receptors. Other dopaminergic syndromes may involve complex functional interactions between D1 and D2 receptors.

Hippocampal Damage: Effects on Dopaminergic Systems of the Basal Ganglia

Although the research topics discussed in this chapter cover a substantial range of areas, methods, and behaviors, there is a consistent central issue: the alterations of brain and behavior subsequent to hippocampal lesions. The initial hypothesis that important secondary changes occur in the basal ganglia after hippocampal lesions has been sustained, at least in part, but other and unexpected results have been obtained that both clarify and mystify at the same time. The restoration of normal locomotion to animals with hippocampal damage by the application of a DAi agonist, DPI, to n. accumbens certainly supports our general idea, but the fact that membrane and transmitter changes in accumbens are transitory needs to be explained and perhaps related to alterations in DA receptor populations. The fact that intra-accumbens DPI can restore ACTH-induced excessive grooming at 28 days after hippocampal damage supports the idea that progressive changes are occurring in DA receptors in n. accumbens, but we need to know their nature more precisely. To do this, however, will probably require advances in our general knowledge of central DA receptors. One of the more interesting aspects of our observations is that the intra-accumbens administration of DPI restores normal behavioral patterns in several types of behaviors, especially locomotion and the excessive grooming response. These two behaviors are not closely linked in nature because large changes can occur in them independently, given appropriate conditions for testing. On the basis of available evidence both of these behaviors seem linked to activities in forebrain DA systems. This would further support the idea that the hippocampus modulates DA activities in basal ganglia systems. The results that suggest the presence of multiple sites for the central induction of grooming were also unexpected. As evidence mounts in support of this idea, it is likely that the one located in n. accumbens is more influenced by hippocampal destruction than the region(s) affected by icv neuropeptide administration. The interactions that take place in the basal ganglia can be extensive. Afferents from the entirety of the neocortical surface, the limbic system, and the projections from the brainstem DA cell groups meet in the striatum and ventral striatum. The efferents from this region not only reach motor cortical and subcortical sites but also project back onto diffusely projecting monoaminergic cells of the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)