Excessive Grooming Behavior Research Articles

Disruption of Astrocyte-Dependent Dopamine Control in the Developing Medial Prefrontal Cortex Leads to Excessive Grooming in Mice

BackgroundAstrocytes control synaptic activity by modulating perisynaptic concentrations of ions and neurotransmitters including dopamine (DA) and, as such, could be involved in the modulating aspects of mammalian behavior. MethodsWe produced a conditional deletion of the vesicular monoamine transporter 2 (VMAT2) specifically in astrocytes (aVMTA2cKO mice) and studied the effects of the lack of VMAT2 in prefrontal cortex (PFC) astrocytes on the regulation of DA levels, PFC circuit functions, and behavioral processes. ResultsWe found a significant reduction of medial PFC (mPFC) DA levels and excessive grooming and compulsive repetitive behaviors in aVMAT2cKO mice. The mice also developed a synaptic pathology, expressed through increased relative AMPA versus NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioral and synaptic phenotypes were rescued by re-expression of mPFC VMAT2 and L-DOPA treatment, showing that the deficits were driven by mPFC astrocytes that are critically involved in developmental DA homeostasis. By analyzing human tissue samples, we found that VMAT2 is expressed in human PFC astrocytes, corroborating the potential translational relevance of our observations in mice. ConclusionsOur study shows that impairment of the astrocytic control of DA in the mPFC leads to symptoms resembling obsessive-compulsive spectrum disorders such as trichotillomania and has a profound impact on circuit function and behaviors.

Erythritol, an Artificial Sweetener, Is Acaricidal Against Pest Mites and Minimally Harmful to a Predatory Mite.

Erythritol, an artificial sweetener, has shown promise as an organic, human-safe insecticide. Recently, erythritol applications were shown to be successful at controlling pear psylla (Cacopsylla pyricola (Förster)) (Hempitera: Psyllidae), the most important pest of pear in the Pacific Northwest, USA. Twospotted spider mite (Tetranychus urticae Koch) (Trombidiformes: Tetranychidae) and pear rust mite (Epitrimerus pyri (Nalepa)) (Trombidiformes: Eriophyidae) can also be highly damaging pear pests. Their common natural enemy, Galendromus occidentalis (Nesbitt) (Mesostigmata: Phytoseiidae), can provide biological control if selective pesticides are used for managing other pests. Through a series of bioassays, we sought to determine whether erythritol could also be used for controlling either species of pest mite. We also examined whether erythritol had acute or sublethal impacts on G. occidentalis, through a variety of exposure methods. Effects examined included mortality, fecundity, prey consumption, and locomotion. We determined that a high concentration of erythritol (30%) had efficacy against both pest mite species and caused arresting behavior in twospotted spider mite. Erythritol caused little acute mortality in G. occidentalis, but did reduce fecundity and prey consumption through some exposure methods. Through motion-capture software, we determined that this is primarily due to reduced movement, likely caused by difficulty walking on residues and excessive grooming behavior. Because the predatory mite non-target effects were less acute than those for the two pest mites, we concluded that erythritol could likely be integrated into pear IPM with little or no disruption of mite biological control.

Implication of the social function of excessive self-grooming behavior in BTBR T+ltpr3tf/J mice as an idiopathic model of autism

Autism spectrum disorder (ASD) is defined by two core behavioral characteristics, namely, restricted repetitive behaviors and impaired social-communicative functioning. BTBR T+ltpr3tf/J (BTBR) mice provide a valuable animal model for ASD to elucidate the underlying mechanisms of these two behavioral characteristics of ASD. This study examined the social function of excessive grooming behavior in BTBR mice as a phenotype of restricted repetitive behaviors. Compared to the control C57BL/6 J (B6) strain, BTBR mice showed increased self-grooming when placed alone in a test apparatus, and this behavior was even more evident when confronted with a stimulus mouse (either B6 or BTBR) in a three-chamber test apparatus. While B6 mice tended to groom their face/snout region on the empty side of the chamber, BTBR mice showed excessive grooming with frequent transitions among grooming body regions on the side of the chamber containing a social stimulus. Acute systemic injection of buspirone,a serotonin 1A receptor agonist, as an anxiolytic, facilitated approach behavior toward social stimuli in the three-chamber setting in both B6 and BTBR mice. However, this treatment did not affect grooming behavior in B6 mice and significantly enhanced self-grooming in BTBR mice. These behaviors in BTBR mice suggest a potential signaling function of grooming in response to social stimuli, in which bodywide grooming of BTBR mice expressed in the proximity of social opponents may stimulate the release of olfactory (possibly dismissive) signals. Consequently, the putative neural mechanisms underlying excessive grooming may differ from those regulating social approaches that are associated with anxiolytic mechanisms.

Genetic Basis of Natural Variation in Spontaneous Grooming in Drosophila melanogaster.

Spontaneous grooming behavior is a component of insect fitness. We quantified spontaneous grooming behavior in 201 sequenced lines of the Drosophila melanogaster Genetic Reference Panel and observed significant genetic variation in spontaneous grooming, with broad-sense heritabilities of 0.25 and 0.24 in females and males, respectively. Although grooming behavior is highly correlated between males and females, we observed significant sex by genotype interactions, indicating that the genetic basis of spontaneous grooming is partially distinct in the two sexes. We performed genome-wide association analyses of grooming behavior, and mapped 107 molecular polymorphisms associated with spontaneous grooming behavior, of which 73 were in or near 70 genes and 34 were over 1 kilobase from the nearest gene. The candidate genes were associated with a wide variety of gene ontology terms, and several of the candidate genes were significantly enriched in a genetic interaction network. We performed functional assessments of 29 candidate genes using RNA interference, and found that 11 affected spontaneous grooming behavior. The genes associated with natural variation in Drosophila grooming are involved with glutamate metabolism (Gdh) and transport (Eaat); interact genetically with (CCKLR-17D1) or are in the same gene family as (PGRP-LA) genes previously implicated in grooming behavior; are involved in the development of the nervous system and other tissues; or regulate the Notch and Epidermal growth factor receptor signaling pathways. Several DGRP lines exhibited extreme grooming behavior. Excessive grooming behavior can serve as a model for repetitive behaviors diagnostic of several human neuropsychiatric diseases.

Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice.

Obsessive-compulsive disorder (OCD) is a circuit disorder involving corticostriatal projections, which play a role in motor control. The Sapap3-knockout (KO) mouse is a mouse model to study OCD and recapitulates OCD-like compulsion through excessive grooming behavior, with skin lesions appearing at advanced age. Deficits in corticostriatal control provide a link to the pathophysiology of OCD. However, there remain significant gaps in the characterization of the Sapap3-KO mouse, with respect to age, specificity of synaptic dysfunction, and locomotor phenotype. We therefore investigated the corticostriatal synaptic phenotype of Sapap3-KO mice using patch-clamp slice electrophysiology, in adult mice and with projection specificity. We also analyzed grooming across age and locomotor phenotype with a novel, unsupervised machine learning technique (MoSeq). Increased grooming in Sapap3-KO mice without skin lesions was age independent. Synaptic deficits persisted in adulthood and involved the projections from the motor cortices and cingulate cortex to the dorsolateral and dorsomedial striatum. Decreased synaptic strength was evident at the input from the primary motor cortex by reduction in AMPA receptor function. Hypolocomotion, i.e., slowness of movement, was consistently observed in Sapap3-KO mice. Our findings emphasize the utility of young adult Sapap3-KO mice to investigate corticostriatal synaptic dysfunction in motor control.

Neuromedin U induces self-grooming in socially-stimulated mice

Emerging evidence suggest that appetite-regulating peptides modulate social behaviors. We here investigate whether the anorexigenic peptide neuromedin U (NMU) modulates sexual behavior in male mice. However, instead of modulating sexual behaviors, NMU administered into the third ventricle increased self-grooming behavior. In addition, NMU-treatment increased self-grooming behavior when exposed to other mice or olfactory social-cues, but not when exposed to non-social environments. As the neuropeptide oxytocin is released during social investigation and exogenous oxytocin induces self-grooming, its role in NMU-induced self-grooming behavior was investigated. In line with our hypothesis, the oxytocin receptor antagonist inhibited NMU-induced self-grooming behavior in mice exposed to olfactory social-cues. Moreover, dopamine in the mesocorticolimbic system is known to be a key regulator of self-grooming behavior. In line with this, we proved that infusion of NMU into nucleus accumbens increased self-grooming behavior in mice confronted with an olfactory social-cue and that this behavior was inhibited by antagonism of dopamine D2, but not D1/D5, receptors. Moreover repeated NMU treatment enhanced ex vivo dopamine levels and decreased the expression of dopamine D2 receptors in nucleus accumbens in socially housed mice. On the other hand, the olfactory stimuli-dependent NMU-induced self-grooming was not affected by a corticotrophin-releasing hormone antagonist, and NMU-treatment did not influence repetitive behaviors in the marble burying test. In conclusion, our results suggest that NMU treatment and, social cues - potentially triggering oxytocin release - together induce excessive grooming behavior in male mice. The mesolimbic dopamine system, including accumbal dopamine D2 receptors, was identified as a crucial downstream mechanism.

T34. Effects of Repeated Cortico-Striatal Optogenetic Stimulation on OCD-Like Behaviors in Rats

Accumulating evidence points to orbitofrontal cortex-ventromedial striatum (OFC-VMS) circuitry hyperactivity in Obsessive-Compulsive Disorder (OCD). Hyper-activating this pathway in inbred mice produces excessive grooming and other perseverative behaviors that outlast the stimulation. We aim to replicate these findings in outbred rats, where there are few reliable models of OCD-related behavior.

Antioxidant Therapies for Ulcerative Dermatitis: A Potential Model for Skin Picking Disorder.

Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine’s mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly tolerated by many patients, intranasal glutathione warrants further study as potential therapy in Skin Picking, trichotillomania and other body-focused repetitive behavior disorders.

Autoimmunity developed in Hoxb8 knock-out mice (P4082)

Abstract Hoxb8 belongs to the homeobox transcription factor family. Hoxb8 knockout (KO) mice exhibit a compulsive grooming, similar to trichotillomania (an impulse control disease) in humans. Hoxb8 is expressed in multiple hematopoietic cells. Bone marrow (BM) cells from Hoxb8 KO are less competitive than wildtype (wt) BM cells in granulocyte/monocyte and T cell lineages, yet more competitive in B cell lineage. How these changes affect development and functions of lymphocytes remain unknown. Here we report that autoimmunity was developed in Hoxb8 KO. Hoxb8 KO sera contain autoantibody against several self-tissues, including brain, kidney and liver. Splenomegaly was found with a higher frequency in KO mice, associating with increased B and T cell numbers. The percentages of surface IgG+ B and activated T cells were significantly increased as well. Moreover, serum IgG levels showed an age-dependent increase: there were trends of increased IgG levels in 3 and 6 month old KO, compared to aged matched wt mice, but all IgG isotypes, except IgG3, were significantly increased in the 9-month-old KO mice. Finally, we showed that autoimmunity developed in Hoxb8 KO mice may not be the major cause of the excessive grooming behavior since compulsive grooming remains in Hoxb8/RAG2 double KO mice. This observation suggests that defects of Hoxb8 in the immune system may play a supportive but not a major role in the pathogenesis of compulsive behavior, which agrees with our microglia hypothesis.

Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat.

Obesity is caused by an imbalance between energy intake and expenditure and has become a major health-care problem in western society. The central melanocortin system plays a crucial role in the regulation of feeding and energy expenditure, and functional loss of melanocortin receptor 4 (MC4R) is the most common genetic cause of human obesity. In this study, we present the first functional Mc4r knockout model in the rat, resulting from an N-ethyl-N-nitrosourea mutagenesis–induced point mutation. In vitro observations revealed impaired membrane-binding and subsequent nonfunctionality of the receptor, whereas in vivo observations showed that functional loss of MC4R increased body weight, food intake, white adipose mass, and changed substrate preference. In addition, intracerebroventricular (ICV) administration of Agouti-Related Protein79–129 (AgRP79–129), an MC4R inverse agonist, or Melanotan-II (MTII), an MC4R agonist, did affect feeding behavior in wild-type rats but not in homozygous mutant rats, confirming complete loss of MC4R function in vivo. Finally, ICV administration of MTII induced excessive grooming behavior in wild-type rats, whereas this effect was absent in homozygous mutant rats, indicating that MTII-induced grooming behavior is exclusively regulated via MC4R pathways. Taken together, we expect that the MC4R rat model described here will be a valuable tool for studying monogenic obesity in humans. More specifically, the relative big size and increased cognitive capacity of rats as compared to mice will facilitate complex behavioral studies and detailed mechanistic studies regarding central function of MC4R, both of which ultimately may help to further understand the specific mechanisms that induce obesity during loss of MC4R function.

Molecular and cellular basis of obsessive–compulsive disorder-like behaviors: emerging view from mouse models

This article reviews recent literature describing novel mouse genetic models of obsessive-compulsive disorder-like behaviors and neurobiological insights gained from analyses of such models. Obsessive-compulsive disorder is a common neuropsychiatric disorder characterized by recurrent intrusive thoughts (obsessions) and ritualistic (compulsive) behaviors. Although the cause of this disorder remains unclear, recent studies of novel mouse genetic models with excessive grooming behaviors have begun to shed light on the molecular and cellular mechanisms underlying the pathogenesis of 'obsessive-compulsive disorder-like' behaviors. Genetic deletion of three genes in mice, Hoxb8, Sapap3, and Slitrk5, leads to pathological behaviors including adult-onset excessive grooming with mild-to-severe hair loss and self-injury. In two of the models, the Sapap3-deficient and the Slitrk5-deficient mice, the abnormal grooming behaviors are associated with enhanced anxiety and these pathological behaviors can be curtailed with subchronic administration of a selective serotonin reuptake inhibitor, suggesting the predictive validity of such models. Molecular, pathophysiological, and genetic analyses of these models reveal several insights on the etiological basis of abnormal behaviors in these mice, including abnormal cortico-striatal synapse formation and function in Sapap3 mice, impaired development and function of bone marrow-derived microglia in Hoxb8 mice, and abnormal striatal neuronal differentiation and neurotransmission in Slitrk5 mice. Novel animal models provide powerful tools to investigate the molecular, cellular, and circuitry mechanisms of obsessive-compulsive disorder-like behaviors. Detailed analyses of these models may provide candidate molecules and mechanisms for the investigation of cause and therapy of obsessive-compulsive disorder.

Comparison of the Spinal Neuropathic Pain Induced by Intraspinal Injection of N-Methyl-D-Aspartate and Quisquate in Rats

Excitatory amino acids play important roles in the development of secondary pathology following spinal cord injury (SCI). This study was designed to evaluate morphological changes in the dorsal horn of the spinal cord and assess profiles of pain behaviors following intraspinal injection of N-methyl-D-aspartate (NMDA) or quisqualate (QUIS) in rats. Forty male Sprague-Dawley rats were randomized into three groups : a sham, and two experimental groups receiving injections of 125 mM NMDA or QUIS into their spinal dorsal horn. Following injection, hypersensitivity to cold and mechanical stimuli, and excessive grooming behaviors were assessed serially for four weeks. At the end of survival periods, morphological changes in the spinal cord were evaluated. Cold allodynia was developed in both the NMDA and QUIS groups, which was significantly higher in the QUIS group than in the NMDA group. The mechanical threshold for the ipsilateral hind paw in both QUIS and NMDA groups was significantly lower than that in the control group. The number of groomers was significantly higher in the NMDA group than in the QUIS group. The size of the neck region of the spinal dorsal horn, but not the superficial layer, was significantly smaller in the NMDA and QUIS groups than in the control group. Intraspinal injection of NMDA or QUIS can be used as an excitotoxic model of SCI for further research on spinal neuropathic pain.

Central Pain from Excitotoxic Spinal Cord Injury Induced by Intraspinal NMDA Injection: A Pilot Study

BackgroundThe pathophysiological and neurochemical changes following spinal injury are not yet elucidated. This study was designed to evaluate the morphological changes of the dorsal horn of the spinal cord and profiles of pain behaviors following intraspinal injection of NMDA in rats.MethodsRats were randomized into three groups: a sham-operated control group and groups where the rats received 10 mM or 100 mM N-methyl-D-aspatate (NMDA) injected into their spinal dorsal horn. Following injection, hypersensitivity to cold and mechanical stimuli and excessive grooming behaviors were assessed serially for four weeks. Morphological changes of the spinal cord were evaluated four weeks after intraspinal injection.ResultsFew animals in the NMDA groups developed hypersensitivity to cold and mechanical stimuli. The number of groomers and the severity of excessive grooming were significantly higher in the 100 mM NMDA group than those values of the control and 10 mM NMDA groups. The size of the neck region (lamina III-IV) was significantly smaller in the 100 mM NMDA group than in the control and 10 mM NMDA groups.ConclusionsIn conclusion, intraspinal injection of NMDA in rats leads to the pathological sequela in the spinal cord and to excessive grooming behavior. These results support the use of NMDA and excessive grooming behavior after excitotoxic SCI as a model to study chronic pain after SCI.

The Mouse Who Couldn't Stop Washing: Pathologic Grooming in Animals and Humans

The basic science literature is replete with descriptions of naturally occurring or experimentally induced pathological grooming behaviors in animals, which are widely considered animal models of obsessive-compulsive disorder (OCD). These animal models rely largely on observed similarities between animal behaviors and human OCD behaviors, and on studies of animal pathological grooming disorders that respond to serotonin enhancing drugs. However, current limitations in assessment of complex cognition and affect in animals precludes the field's ability to match the driving primary processes behind observable phenomenology in animal "OCD" with human behavioral disorders. We propose that excessive grooming behaviors in animals may eventually prove to be equally, or possibly more relevant to, other conditions in humans that involve pathological grooming or grooming-like behaviors, such as trichotillomania, body dysmorphic disorder, olfactory reference syndrome, compulsive skin-picking, and onychophagia. Research is needed to better understand pathological grooming behaviors in both humans and animals, as animal models have the potential to elucidate pathogenic mechanisms and inform the treatment of these psychiatric conditions in humans.

Predifferentiated Embryonic Stem Cells Prevent Chronic Pain Behaviors and Restore Sensory Function Following Spinal Cord Injury in Mice

Embryonic stem (ES) cells have been investigated in repair of the CNS following neuronal injury and disease; however, the efficacy of these cells in treatment of postinjury pain is far from clear. In this study, we evaluated the therapeutic potential of predifferentiated mouse ES cells to restore sensory deficits following spinal cord injury (SCI) in mice. The pain model used unilateral intraspinal injection of quisqualic acid (QUIS) into the dorsal horn between vertebral levels T13 and L1. Seven days later, 60,000 predifferentiated ES cells or media were transplanted into the site of the lesion. Histological analysis at 7, 14, and 60 days post-transplantation revealed that animals receiving ES cell transplants suffered significantly less tissue damage than animals receiving media alone. Transplanted cells provided immediate effects on both spontaneous and evoked pain behaviors. Treatment with ES cells resulted in 0% (n = 28) excessive grooming behavior versus 60% (18 of 30) in media-treated animals. In the acetone test (to assess thermal allodynia), mice recovered to preinjury levels by 12 days after ES cell transplant, whereas control animals injected with media after SCI did not show any improvement up to 60 days. Similarly, the von Frey test (to assess mechanical allodynia) and the formalin test (to assess nociceptive hyperalgesia) showed that transplantation of predifferentiated ES cells significantly reduced these pain behaviors following injury. Here we show that predifferentiated ES cells act in a neuroprotective manner and provide antinociceptive and therapeutic effects following excitotoxic SCI.

Activation of the ERK1/2 signaling cascade by excitotoxic spinal cord injury

The role of the ERK1/2 signal transduction pathway and related transcription factors in the regulation of gene expression and pain behavior following excitotoxic spinal cord injury (SCI) was examined. Specifically, phosphorylation of ERK1/2, activation of transcription factors NF-kB, ELK-1, and CREB, and gene expression of the neurokinin-1 receptor and NMDA receptor subunits NR1 and NR-2A were investigated. Excitotoxic injury was produced by intraspinal injection of quisqualic acid (QUIS) in male Sprague–Dawley rats. Western blots were used to evaluate phosphorylation and activation of ERK1/2 and transcription factors using phospho-specific or total antibodies. Real-time PCR was used to evaluate gene expression of NK-1R, NR-1, and NR-2A. Assessment of excessive grooming behavior was used to evaluate the presence of spontaneous pain behavior. Excitotoxic spinal injury resulted in: (1) increased phosphorylation of ERK1/2; (2) increased activation of NF-kB and phosphorylation of ELK-1; and (3) increased gene expression for the NK-1 receptor and NR1 and NR-2A subunits of the NMDA receptor. Blockade of the ERK cascade with the MEK inhibitor PD98059 inhibited phosphorylation of ELK-1, activation of NF-kB and gene expression of NR1, NR-2A and NK-1R, and prevented the development of excessive grooming behavior. The results have shown that excitotoxic spinal injury leads to the injury-induced activation of the ERK→ELK-1 and NF-kB signaling cascades and transcriptional regulation of receptors important in the development of chronic pain. Blockade of this intracellular kinase cascade prevented the onset of injury-induced pain behavior.

Peptoid−Peptide Hybrids as Potent Novel Melanocortin Receptor Ligands

All possible peptoid-peptide hybrids of an MC4 receptor agonist were synthesized and investigated on cells expressing different melanocortin (MC) receptor subtypes and for rat grooming behavior. In general, receptor selectivity remained while affinity and potency were decreased. The length of the functional group of Trp was more important for MC3 and MC5 than for MC4 receptor binding. In general, the potency of the peptoid-peptide hybrids to increase rat excessive grooming behavior correlated well with MC4 receptor pharmacology.

N-Methyl- d-aspartate receptor subunit expression and phosphorylation following excitotoxic spinal cord injury in rats

The role of NMDA receptor expression and post-translational modification in the pathological and behavioral consequences of injury were examined in rats receiving spinal injections of quisqualate. Spinal cords were removed 3 days following the development of excessive grooming behavior or, if the spontaneous pain-like behavior was not observed, 13 days following injections. Western blots from the spinal tissue demonstrated that non-grooming animals had elevated protein levels of the NR1 subunit of the NMDA receptor. These subunits did not demonstrate an enhanced level of phosphorylation. NR1 protein in grooming rats was not elevated, but there was a significant increase in NR1 serine phosphorylation. These findings suggest that excitotoxic lesions of the spinal cord induce both NR1 expression and NR1 serine phosphorylation. However, the injury-induced excessive grooming behavior is only associated with phosphorylation of the NR1 subunit.

Effects of agmatine, interleukin-10, and cyclosporin on spontaneous pain behavior after excitotoxic spinal cord injury in rats

Intraspinal injection of the AMPA/metabotropic receptor agonist quisqualic acid (QUIS) results in a pathophysiology that leads to excessive grooming behavior, which has been proposed as a model of spontaneous at-level pain after spinal cord injury (SCI). To further characterize the onset and progression of this behavior we evaluated the effects of 3 drugs, agmatine (Agm), interleukin-10 (IL-10), and cyclosporin A (CsA), on different characteristics of this behavior. In these experiments rats were given saline, Agm, CsA10, or CsA20 once daily for 14 days (or a single injection of IL-10) starting either 30 minutes post-QUIS (group 1) or 10 to 18 days post-QUIS when excessive grooming behavior had been established (group 2). In the first group of animals agmatine, IL-10, CsA10, or CsA20 reduced the longitudinal extent of neuronal loss in the spinal cord compared to QUIS-injected animals treated with saline. The behavioral consequences of this effect included the delayed onset of excessive grooming behavior, reduction in the area of skin targeted for excessive grooming, and reduced grooming severity. Animals treated at the time of excessive grooming onset showed significantly reduced grooming area, grooming severity, and neuronal loss in the spinal cord compared to QUIS animals treated with saline. In conclusion, systemic administration of Agm, IL-10, or CsA significantly delayed the onset and reduced the severity of a spontaneous pain-like behavior. These effects are believed to be due, in part, to the neuroprotective properties of these drugs against QUIS-induced excitotoxicity. The effective treatment of excessive grooming behavior suggests that Agm, IL-10, and CsA modulate ongoing cellular events responsible for the progression of this behavior. [copy ] 2003 by the American Pain Society

Participation of the cholinergic system in the excessive grooming behavior induced by neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI).

The neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI) injected into the ventral tegmental area (VTA) or intraventricularly (icv) induces excessive grooming behavior (EGB) and motor activity (MA). Here, we studied whether the cholinergic system is involved in the NEI-induced behavior. The present results demonstrate that atropine, a general muscarinic antagonist, injected icv previous to NEI, suppresses the behavior provoked by icv injections of the peptide, whereas the prior icv injection of dyhidro-beta-erythroidine, a general nicotinic antagonist, did not affect the EGB and MA induced by the peptide. From the experimental evidence, it is suggested that NEI may act specifically on a cholinergic afferent to dopaminergic cells. Also, the results appear to indicate that a neural target, different from the dopamine system, may be activated by the peptide to elicit behavioral changes, such as EGB.