Spontaneous Grooming Research Articles

Chronic administration of low dose aspirin alleviates ASD-like behaviors and activates AMPK in valproic acid-exposed rats

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder distinguished by deficits in social communication and the presence of restricted/repetitive behaviors. There has been a global increase in the prevalence of ASD, yet the underlying causes of ASD remain inadequately understood, and there is currently no pharmacological intervention for the core symptoms of ASD. However, recent studies have suggested that aspirin may have the potential for use in the treatment of ASD. MethodPregnant rats were administered either VPA or normal saline on gestational day 12.5. The male pups were administered a low dose of aspirin (1 mg/kg) or a vehicle control daily from postnatal day 23 to day 52. ASD-like behaviors were assessed by social interaction, spontaneous grooming test, open field test and light-dark transitions. The activity of AMP-activated protein kinase (AMPK) was quantified by measuring the level of p-AMPK using an immunoblotting assay. ResultsChronic administration of low dose aspirin resulted in significant improvements in social approach deficits, a reduction in repetitive grooming, and the alleviation of anxiety-like behavior in ASD rats. Furthermore, aspirin administration also led to the activation of AMPK in the hippocampus of rats exposed to VPA. ConclusionsThese results raise the question of the need for further investigation of agents with mechanisms related to aspirin in ASD.

Neurofibromin deficiency alters the patterning and prioritization of motor behaviors in a state-dependent manner.

Genetic disorders such as neurofibromatosis type 1 increase vulnerability to cognitive and behavioral disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Neurofibromatosis type 1 results from loss-of-function mutations in the neurofibromin gene and subsequent reduction in the neurofibromin protein (Nf1). While the mechanisms have yet to be fully elucidated, loss of Nf1 may alter neuronal circuit activity leading to changes in behavior and susceptibility to cognitive and behavioral comorbidities. Here we show that mutations decreasing Nf1 expression alter motor behaviors, impacting the patterning, prioritization, and behavioral state dependence in a Drosophila model of neurofibromatosis type 1. Loss of Nf1 increases spontaneous grooming in a nonlinear spatial and temporal pattern, differentially increasing grooming of certain body parts, including the abdomen, head, and wings. This increase in grooming could be overridden by hunger in food-deprived foraging animals, demonstrating that the Nf1 effect is plastic and internal state-dependent. Stimulus-evoked grooming patterns were altered as well, with nf1 mutants exhibiting reductions in wing grooming when coated with dust, suggesting that hierarchical recruitment of grooming command circuits was altered. Yet loss of Nf1 in sensory neurons and/or grooming command neurons did not alter grooming frequency, suggesting that Nf1 affects grooming via higher-order circuit alterations. Changes in grooming coincided with alterations in walking. Flies lacking Nf1 walked with increased forward velocity on a spherical treadmill, yet there was no detectable change in leg kinematics or gait. Thus, loss of Nf1 alters motor function without affecting overall motor coordination, in contrast to other genetic disorders that impair coordination. Overall, these results demonstrate that loss of Nf1 alters the patterning and prioritization of repetitive behaviors, in a state-dependent manner, without affecting motor coordination.

Ventral striatal islands of Calleja neurons control grooming in mice.

The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely-packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons, SPNs), whose firing rates display grooming-related modulation. Our study uncovers a novel role of the ventral striatum’s IC in regulating motor output and has important implications for the neural control of grooming.

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.

Blockade of peripheral endothelin receptors abolishes heat hyperalgesia and spontaneous nociceptive behavior in a rat model of facial cancer

ObjectiveTo improve understanding of the pathophysiology of cancer-induced facial nociception, by evaluating the contribution of peripheral endothelin receptors in tumor-induced facial heat hyperalgesia, increased spontaneous grooming, as well as ongoing nociception in a rat model of facial cancer. DesignThe study was conducted using 396 rats. Facial cancer was induced by inoculating a suspension of Walker-256 cells into the rats’ right vibrissal pad. Facial heat hyperalgesia and spontaneous grooming were assessed on day 6, while the conditioned place preference (CPP) test was performed on days 3–6 after tumor cells inoculation. Rats received local injections of the non-peptidic dual ETA/ETB endothelin receptors antagonist, bosentan (10 and 30 μg/50 μL), single or combined injections of peptidic ETA and ETB endothelin receptors antagonists (BQ-123 and BQ-788, at 20 ug/50 μL, each), or of lidocaine (1 mg/50 μl) and morphine (30 μg/50 μL). ResultsBosentan, lidocaine and morphine local treatment all attenuated tumor-induced heat hyperalgesia (p < 0.05) and spontaneous facial grooming (p < 0.05). However, BQ-123 and BQ-788 did not modify tumor-induced heat hyperalgesia or the spontaneous facial grooming (p > 0.05). Whether this difference in effectiveness is due to receptor affinity or to pharmacokinetic factors still needs to be explored. Local injection of bosentan, lidocaine or morphine failed to control ongoing nociception, as evidenced by the absence of CPP in tumor-bearing rats (p > 0.05). ConclusionEndothelins, acting through peripheral ETA and ETB receptors, may play a significant role on the development of heat hyperalgesia and increased spontaneous grooming associated to facial cancer in rats.

Blockade of endothelin receptors reduces tumor-induced ongoing pain and evoked hypersensitivity in a rat model of facial carcinoma induced pain

Pain reported by patients with head and neck cancer is characterized as persistent pain with mechanical allodynia. Pain management is inadequate for many patients, highlighting the need for improved therapies. We examined the hypothesis that the mixed endothelin ETA and ETB receptor antagonist, bosentan, reduces tumor-induced ongoing pain and evoked hypersensitivity in a rat model of facial cancer pain. Facial cancer was induced by inoculating a suspension of Walker-256 cells into the rat's right vibrissal pad. Tumor-bearing rats developed heat and tactile hypersensitivity along with increased spontaneous grooming behavior. Systemic morphine (2.5mg/kg, s.c.) blocked tumor-induced thermal and tactile hypersensitivity, with a lower dose (0.625mg/kg, s.c.) effective only against thermal hypersensitivity. Systemic bosentan blocked tumor-induced thermal hypersensitivity only at a high (300mg/kg, p.o.) dose, but failed to modify tactile hypersensitivity. Co-administration of the low doses of bosentan and morphine resulted in improved reduction of the tumor-induced heat and tactile hypersensitivity compared to either dose alone. Bosentan (100mg/kg, p.o.) reduced spontaneous grooming and induced conditioned place preference (CPP) selectively in tumor-bearing rats, suggesting that bosentan reduces tumor-induced ongoing pain at a lower dose than required to block tumor-induced hypersensitivity. This study provides evidence that endothelins may mediate tumor-induced ongoing pain and thermal hypersensitivity. In addition, bosentan enhanced morphine's effects on blocking tumor-induced heat and tactile hypersensitivity indicating that endothelin antagonists may be beneficial therapeutic targets that can be used to manage cancer-induced facial pain with opioid-sparing effects.

M-Track: A New Software for Automated Detection of Grooming Trajectories in Mice

Grooming is a complex and robust innate behavior, commonly performed by most vertebrate species. In mice, grooming consists of a series of stereotyped patterned strokes, performed along the rostro-caudal axis of the body. The frequency and duration of each grooming episode is sensitive to changes in stress levels, social interactions and pharmacological manipulations, and is therefore used in behavioral studies to gain insights into the function of brain regions that control movement execution and anxiety. Traditional approaches to analyze grooming rely on manually scoring the time of onset and duration of each grooming episode, and are often performed on grooming episodes triggered by stress exposure, which may not be entirely representative of spontaneous grooming in freely-behaving mice. This type of analysis is time-consuming and provides limited information about finer aspects of grooming behaviors, which are important to understand movement stereotypy and bilateral coordination in mice. Currently available commercial and freeware video-tracking software allow automated tracking of the whole body of a mouse or of its head and tail, not of individual forepaws. Here we describe a simple experimental set-up and a novel open-source code, named M-Track, for simultaneously tracking the movement of individual forepaws during spontaneous grooming in multiple freely-behaving mice. This toolbox provides a simple platform to perform trajectory analysis of forepaw movement during distinct grooming episodes. By using M-track we show that, in C57BL/6 wild type mice, the speed and bilateral coordination of the left and right forepaws remain unaltered during the execution of distinct grooming episodes. Stress exposure induces a profound increase in the length of the forepaw grooming trajectories. M-Track provides a valuable and user-friendly interface to streamline the analysis of spontaneous grooming in biomedical research studies.

Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila.

Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits.

Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats

We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings.

Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autistic-like stereotypical behaviors in offspring mice

Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypical behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior.

D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling

The genetically inbred BTBR T+ Itpr3tf/J (BTBR) mouse is a proposed model of autism spectrum disorders (ASDs). Similar to several syndromic forms of ASDs, mTOR activity may be enhanced in this mouse strain as a result of increased Ras signaling. Recently, D-cycloserine, a partial glycineB site agonist that targets the NMDA receptor, was shown to improve the sociability of the Balb/c mouse strain, another proposed genetically inbred model of ASDs. NMDA receptor activation is an important regulator of mTOR signaling activity. Given the ability of D-cycloserine to improve the sociability of the Balb/c mouse strain and the regulatory role of the NMDA receptor in mTOR signaling, we wondered if D-cycloserine would improve the impaired sociability of the BTBR mouse strain. D-Cycloserine (320 mg/kg, ip) improved measures of sociability in a standard sociability paradigm and spontaneous grooming that emerged during social interaction with an ICR stimulus mouse in the BTBR strain; however, similar effects were observed in the Swiss Webster comparator strain, raising questions about their strain-selectivity. Importantly, the profile of D-cycloserine's effects on both measures of sociability and stereotypies is consistent with that of a desired medication for ASDs; specifically, a desired medication would not improve sociability at the expense of worsening stereotypic behaviors or vice versa.

The BTBR T+tf/J (BTBR) Mouse Model of Autism

Mouse models of neuropsychiatric disorders are validated according to three different criteria: face validity, construct validity and predictive validity. Autism Spectrum Disorders (ASDs) are diagnosed behaviorally, therefore, mouse models of ASDs rely primarily on face validity. The three diagnostic criteria for ASDs are impairments in social interaction, communication and repetitive behavior, and/or restricted interests. The BTBR T+tf/J (BTBR) mice are an inbred strain used as model of ASDs. All three types of behavioral criteria have been evaluated in the BTBR mice. An advantage of using an inbred strain, such as BTBR is that, the mice are considered genetically identical and offer good controls for experimentation. The BTBR mice have demonstrated face validity for the three core behaviors that define ASDs. Low levels of social behavior, altered communication and spontaneous grooming comprise the behavioral phenotype of the BTBR mice. For construct validity, the BTBR mice have some physiological characteristics similar to humans with ASDs. Several drug and behavioral treatments for ASDs have been examined in the BTBR mice; however this area of research is still being developed. This review will offer a description of the behavior and physiology of the BTBR mice as a model for ASDs.

Cocaine effects on behavioral responding to a novel object placed in a familiar environment

It is well established that cocaine stimulant effects are potentiated in a novel environment. The relationship between cocaine and novel stimuli, however, remains poorly understood. In this study, we examined the effects of different dose levels of cocaine (5.0, 10.0 and 20.0 mg/kg) administered to separate groups of rats ( N = 10) on attentional behavior to a small novel object stimulus placed within a central zone (CZ) of a familiar open-field environment. This method has been used to assess attentional function in young animals, brain damaged animals and drug treated animals. In previous studies, we have shown that attention to a novel object stimulus can be quantified by an animal's contact time with the object. Following a series of pre-exposures to the test environment without the novel object, we found that cocaine in a brief 10 min test session with the novel object present produced a dose related decrease in mean contact time with the novel object. In contrast caffeine (5.0, 10.0 and 20.0 mg/kg), which induced a locomotor stimulant effect equivalent to cocaine, did not impair novel object contact time. Correlational analyses indicated absence of significant negative correlation coefficients of locomotor activity and contact time with the novel object. These considerations indicate that the observed cocaine impairment of attention to the novel stimulus is not attributable to hyperactivity per-se. Furthermore, cocaine, but not caffeine, induced a dose related decrease in the duration of spontaneous grooming. Thus, cocaine appears to diminish an animal's overall capability to maintain a behavioral process (i.e., investigate a novel object stimulus and/or engage in spontaneous bodily directed activity such as grooming). Altogether, the findings obtained in the present study indicate that cocaine impairs an animal's ability to sustain attention to stimuli and suggest a behavioral state analogous to an attention deficit disorder.

Contrasting grooming phenotypes in three mouse strains markedly different in anxiety and activity (129S1, BALB/c and NMRI)

129S1/SvImJ (129S1), NMRI and BALB/c mice are widely used in behavioural research, demonstrating marked strain differences in their behavioural phenotypes. Grooming is a complex and essential ritual in the rodent behavioural repertoire with a general cephalocaudal progression (forepaws–nose–face–body–legs–tail and genitals). Various stressors as well as genetic manipulations have been reported to alter mouse grooming and its patterning, underlying the importance of analysis of grooming behaviours. Although strain differences between these mice have been assessed in many studies, no comparative analyses of their grooming have been performed. Here we show strain differences in spontaneous (novelty-induced) grooming between 129S1, NMRI and BALB/c mice. Overall, 129S1 mice demonstrated lower grooming activity and impaired microstructure (more interrupted bouts and incorrect transitions contrary to the cephalocaudal rule), accompanied by lower vertical exploration. In contrast, BALB/c and NMRI mice showed high vertical activity and unimpaired grooming microstructure, also exhibiting different grooming levels (BALB/c > NMRI). Our study suggests that contrasting grooming phenotypes in these mice may not be due to the strain differences in their sensory abilities, general activity levels, brain anatomy or aggressiveness, but rather reflect a complex interplay between anxiety, motor and displacement activity in these strains (hypoactive anxious phenotype in 129S1 mice, active anxious phenotype in BALB/c and non-anxious high displacement phenotype in NMRI mice). We suggest that ethological analysis of mouse grooming, such as that reported here, may be a useful tool in neurobehavioural research.

Nicotine-induced grooming: a possible dopaminergic and/or cholinergic mechanism.

The ability of nicotine, to induce grooming in rats was studied. Grooming was induced by i.p. injection of different doses (0.0675-0.5 mg/kg) of nicotine to rats. The effect was dose-dependent. However, the response was decreased with increasing doses of the drug from 0.25-0.5 mg/kg. Administration of the dopamine (DA) D1/D2 receptor agonist apomorphine (0.025-5 mg/kg, i.p.) also caused grooming in a dose-dependent manner. High doses of apomorphine (0.1-0.5 mg/kg, i.p.) also induced a lower degree of response. Combination of a low dose of nicotine (0.0675 mg/kg) with different doses of apomorphine did not show any interaction. However, there was an interaction between a high dose of nicotine and apomorphine. Thus, combination of a higher dose of nicotine (0.125 mg/kg) with apomorphine, reduced apomorphine-induced grooming. The muscarinic receptor antagonist atropine (5 and 10 mg/kg), peripheral nicotinic receptor antagonist hexamethonium (5 and 10 mg/kg), central nicotinic receptor antagonist mecamylamine (1 and 3 mg/kg) and D1 DA receptor antagonist SCH23390 (0.05 and 0.1 mg/kg) all decreased the response to nicotine. Atropine, mecamylamine and SCH23390 by themselves reduced spontaneous grooming. It is concluded that nicotine elicits grooming indirectly through a possible D1 dopaminergic mechanism. However, muscarinic and nicotinic cholinergic mechanism(s) may be involved.

Effect of NMDA receptor antagonists on D1, D2 and D1/D2 mediated behaviors in intact rats.

The effect of treatment with the competitive (CGP 43487) and non-competitive (MK-801) NMDA antagonists on behaviors induced by the stimulation of D1 (SKF 38393 induced grooming), D2 (LY 171555 elicited hypermotility) or D1/D2 (apomorphine induced locomotion and stereotypies) was observed in intact rats. The administration of low doses of MK-801 (0.03 and 0.06 mg/kg) or CGP 43487 (0.375 and 0.75 mg/kg), which were without effect by themselves on animal locomotion, reduced the hyperactivity induced by LY 171555 (0.15 mg/kg) and did not change the stimulating motor effect of a low dose of apomorphine (0.15 mg/kg). Spontaneous grooming behavior was inhibited by both NMDA antagonists, whereas the administration of CGP 43487 but not of MK-801 potentiated grooming response to SKF 38393 (10 mg/kg). Both antagonists increased stereotyped behavior induced by 0.25 mg/kg apomorphine. The results, according to those obtained by other authors in DA depleted/lesioned animals, support the view of interaction between NMDA/D1,D2 receptors in intact rats.

The dopamine D 1 receptor agonists, A68930 and SKF 38393, induce arousal and suppress REM sleep in the rat

The effects of the dopamine D 1 receptor full agonist, A68930, on sleep-wake patterns and grooming behavior were studied in the rat. The partial dopamine D 1 receptor agonist, SKF 38393, was used for comparison. A68930 (0.003–0.3 mg/kg s.c.) increased waking time, reduced the amount of rapid eye movement (REM) sleep and enhanced spontaneous grooming dose dependently. The ED 50 were 0.06, 0.02 and 0.05 mg/kg, respectively. The D 1 antagonist, SCH 23390 (0.003 mg/kg s.c.), blocked the effects of A68930 on wakefulness and grooming but not those on REM sleep. SKF 38393 (0.1–10 mg/kg s.c.) increased grooming with an ED 50 of 1.4 mg/kg and a dose-response relationship similar to that of A68930 (potency ratio 28). Conversely, the increase of wakefulness and reduction of REM sleep caused by SKF 38393 had dose-response curves different from those of A68930. The results support the view that D 1 receptors may have a physiological function in producing arousal.

Randomness in Ontogeny. On Antennal Grooming in the Milkweed Bug Oncopeltus fasciatus

AbstractMilkweed bugs (Oncopeltus fasciatus, Lygaeidae) groom the distal segment of each antenna between the tibial combs of both forelegs. Variable numbers of grooming strokes compose a grooming bout. A total of 112 spontaneous grooming bouts, comprising all developmental stages, were videotaped, the angular movements of the forelegs were digitized, and the outcomes computer‐analyzed. Individual strokes of forelegs were measured by their angular amplitude and mean angular elevation. These two measures are randomly combined in the first instar and then differentiate during ontogeny into two distinct types: small amplitude strokes of high average elevation and large amplitude strokes of lower average elevation. The sequencing of small and large strokes within bouts is largely (97%) random in all developmental stages. The outcome of the analysis fits the general empirical rule that premature action patterns are more random than mature ones. Some traits do not follow this rule and are persistently highly random. It is suggested that excessive randomness in premature behavior is due to genetic underdetermination, and that incorporation of non‐genetic information helps to specify the less random mature behavior. Developmentally persistent behavioral randomness is explained by the behavioral‐entropy principle: traits in behavior vary randomly unless randomness is selected against.

Standardization for determining image quality in thermal neutron radiographic testing : Yamagata, H.; Yoneda, K.; Fujine, S.; Kanda, K.; Katsurayama, K. Annual reports of the research reactor Institute Kyoto University, Vol. 19, pp. 116–123 (1986)

It is well established that cocaine stimulant effects are potentiated in a novel environment. The relationship between cocaine and novel stimuli, however, remains poorly understood. In this study, we examined the effects of different dose levels of cocaine (5.0, 10.0 and 20.0 mg/kg) administered to separate groups of rats (N = 10) on attentional behavior to a small novel object stimulus placed within a central zone (CZ) of a familiar open-field environment. This method has been used to assess attentional function in young animals, brain damaged animals and drug treated animals. In previous studies, we have shown that attention to a novel object stimulus can be quantified by an animal's contact time with the object. Following a series of pre-exposures to the test environment without the novel object, we found that cocaine in a brief 10 min test session with the novel object present produced a dose related decrease in mean contact time with the novel object. In contrast caffeine (5.0, 10.0 and 20.0 mg/kg), which induced a locomotor stimulant effect equivalent to cocaine, did not impair novel object contact time. Correlational analyses indicated absence of significant negative correlation coefficients of locomotor activity and contact time with the novel object. These considerations indicate that the observed cocaine impairment of attention to the novel stimulus is not attributable to hyperactivity per-se. Furthermore, cocaine, but not caffeine, induced a dose related decrease in the duration of spontaneous grooming. Thus, cocaine appears to diminish an animal's overall capability to maintain a behavioral process (i.e., investigate a novel object stimulus and/or engage in spontaneous bodily directed activity such as grooming). Altogether, the findings obtained in the present study indicate that cocaine impairs an animal's ability to sustain attention to stimuli and suggest a behavioral state analogous to an attention deficit disorder.

Natural syntax rules control action sequence of rats

Knowledge of the principles by which behavioral sequences are generated is essential to progress in our understanding of neural mechanisms. We describe here a set of natural principles or syntax rules that organize the components of grooming and feeding. The behavioral stream of facial grooming or of taste-elicited ingestive/aversive consummatory actions of rats can be viewed as a long series of individual movements linked together to form functional sequences. In order to ascertain the syntax rules that determine how these actions are linked together, many thousands of spontaneous grooming and elicited ingestive/aversive actions were videotaped and scored with a microcomputer. Techniques of information analysis of sequential stereotypy, tabulation of the sequential transitions between single actions and between action groups, and visual inspection for linear action chains, were employed to expose underlying rules of behavioral sequencing. These analyses revealed two global patterns: action perseveration and transitional reciprocation between sequential pairs and triplets, which together account for approximately 75% of all sequential transitions during grooming and ingestion/aversion. The pattern of transitional reciprocation could be divided further into patterns of alternation between individual actions on the one hand, and between perseverating bouts of actions on the other. Global syntax rules applied equally to actions emitted during grooming or during taste-elicited ingestion/aversion. In addition, a specific rule of linear chaining was found to apply only to facial grooming. These natural rules of action syntax provide insight into the sequential structure of behavior, and lend themselves well to analyses of neural mechanisms.