Behavioral mirroring in Wistar rats investigated through temporal pattern analysis.

The study of social interactions lies at the core of several disciplines such as psychiatry, psychology and ethology, just to name a few. In this context, understanding the temporal patterns underlying interactive behaviors is of crucial importance. Here, we employed T-pattern detection and analysis to study social interactions in ten pairs of Wistar rats tested in an Open-Field environment. We found four different categories of interactive behaviors. One of them was of particular interest to us because it consisted of behavioral events that, taken individually, should not underlie an interaction of any kind; however, they were included in T-patterns, which is suggestive of a dyadic temporal coordination in the behavioral expression of two individuals. Within this category, we described for the first time a new subcategory of apparent interaction patterns characterized by events that one of the two rats repeats only if previously produced by the partner (i.e., behavioral mirroring). These findings are discussed in functional terms for rodents and in light of our current understanding of social interactions in humans.

Sex-dependent behavioral effects of chronic nicotine during adolescence evaluated in young adult rats tested in Hole-Board.

As one of the leading causes of death and serious illnesses, tobacco smoking remains a significant issue in modern societies. Many individuals smoke during adolescence, a trend that has been exacerbated by the prevalence of vaping among young people. In this context, studying the behavioral effects induced by nicotine administration in male and female rats, during the adolescent period, assumes great importance because it can help to better understand the dynamics underlying tobacco use in the two sexes. For this purpose, we employed 4 groups of rats, 2 male and 2 female groups, chronically treated with saline or nicotine 3 mg/kg i.p. for 30 days, spanning from postnatal day 30 to postnatal day 60. Utilizing quantitative analyses and T-pattern detection and analysis, our findings revealed a complex and multifaceted behavioral reorganization in adolescent rats subjected to chronic nicotine administration. Specifically, we observed an increase of anxiety in males and a reduction in females. The distinctive structural changes, induced by chronic nicotine in both sexes, have significant implications, from a translational perspective, for studies on nicotine dependence disorders.

A quantitative and T-pattern analysis of anxiety-like behavior in male GAERS, NEC, and Wistar rats bred under the same conditions, against a commercially available Wistar control group in the hole board and elevated plus maze tests.

AIM: The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbred polygenic model of childhood absence epilepsy (CAE), which, as their non-epileptic control (NEC) rats, are derived from Wistar rats. While the validity of GAERS in reproducing absence seizures is well established, its use as a model for CAE psychiatric comorbidities has been subject to conflicting findings. Differences in colonies, experimental procedures, and the use of diverse controls from different breeders may account for these disparities. Therefore, in this study, we compared GAERS, NEC, and Wistar bred in the same animal facility with commercially available Wistar (Cm Wistar) as a third control. METHODS: We performed hole board (HB) and elevated plus maze (EPM) tests that were analyzed with standard quantitative and T-pattern analysis in male, age-matched Cm Wistar and GAERS, NEC, and Wistar, bred under the same conditions, to rule out the influence of different housing factors and provide extra information on the structure of anxiety-like behavior of GAERS rats. RESULTS: Quantitative analysis showed that GAERS and NEC had similar low anxiety-like behavior when compared to Cm Wistar but not to Wistar rats, although a higher hole-focused exploration was revealed in NEC. T-pattern analysis showed that GAERS, NEC, and Wistar had a similar anxiety status, whereas GAERS and NEC exhibited major differences with Cm Wistar but not Wistar rats. EPM results indicated that GAERS and NEC also have similar low anxiety compared to Cm Wistar and/or Wistar rats. Nevertheless, the analysis of the T-pattern containing open-arm entry showed GAERS and Wistar to be less anxious than NEC and Cm Wistar rats. CONCLUSION: To summarize, comorbid anxiety may not be present in male GAERS rats. This study also highlighted the importance of including a control Wistar group bred under the same conditions when evaluating their behavior, as using Wistar rats from commercial breeders can lead to misleading results.

The hole-board apparatus in the study of anxiety.

Anxiety disorders pose a significant challenge in contemporary society, and their impact in terms of social and economic burden is overwhelming. Behavioral research conducted on animal subjects is crucial for comprehending these disorders and, from a translational standpoint, for introducing innovative therapeutic approaches. In this context, the Hole-Board apparatus has emerged as a widely utilized test for studying anxiety-related behaviors in rodents. Although a substantial body of literature underscores the utility and reliability of the Hole-Board in anxiety research, recent decades have witnessed a range of studies that have led to uncertainties and misinterpretations regarding the validity of this behavioral assay. The objective of this review is twofold: firstly, to underscore the utility and reliability of the Hole-Board assay, and concurrently, to examine the underlying factors contributing to potential misconceptions surrounding its utilization in the study of anxiety and anxiety-related behaviors. We will present results from both conventional quantitative analyses and multivariate approaches, while referencing a comprehensive collection of studies conducted using the Hole-Board.

Structural analyses in the study of behavior: From rodents to non-human primates.

The term "structure" indicates a set of components that, in relation to each other, shape an organic complex. Such a complex takes on essential connotations of functionally unitary entity resulting from the mutual relationships of its constituent elements. In a broader sense, we can use the word "structure" to define the set of relationships among the elements of an emergent system that is not determined by the mere algebraic sum of these elements, but by the interdependence relationships of these components from which the function of the entire structure itself derives. The behavior of an integrated living being can be described in structural terms via an ethogram, defined as an itemized list of behavioral units. Akin to an architectural structure, a behavioral structure arises from the reciprocal relationships that the individual units of behavior establish. Like an architectural structure, the function of the resulting behaving complex emerges from the relationships of the parts. Hence, studying behavior in its wholeness necessitates not only the identification of its constitutive units in their autarchic individuality, but also, and importantly, some understanding of their relationships. This paper aimed to critically review different methods to study behavior in structural terms. First, we emphasized the utilization of T-pattern analysis, i.e., one of the most effective and reliable tools to provide structural information on behavior. Second, we discussed the application of other methodological approaches that are based on the analysis of transition matrices, such as hierarchical clustering, stochastic analyses, and adjusted residuals. Unlike T-pattern analysis, these methods allow researchers to explore behavioral structure beyond its temporal characteristics and through other relational constraints. After an overview of how these methods are used in the study of animal behavior, from rodents to non-human primates, we discussed the specificities, advantages and challenges of each approach. This paper could represent a useful background for all scientists who intend to study behavior both quantitatively and structurally, that is in terms of the reciprocal relationships that the various units of a given behavioral repertoire normally weave together.

Cannabinoid 1/2 Receptor Activation Induces Strain-Dependent Behavioral and Neurochemical Changes in Genetic Absence Epilepsy Rats From Strasbourg and Non-epileptic Control Rats.

Childhood absence epilepsy (CAE) is characterized by absence seizures, which are episodes of lack of consciousness accompanied by electrographic spike-wave discharges. About 60% of children and adolescents with absence seizures are affected by major neuropsychological comorbidities, including anxiety. Endocannabinoids and monoamines are likely involved in the pathophysiology of these CAE psychiatric comorbidities. Here, we show that the synthetic cannabinoid receptor type 1/2 (CB1/2R) agonist WIN 55,212-2 (2 mg/kg) has a strain-dependent effect on anxiety-like and motor behavior when assess in the hole board test and cerebral monoaminergic levels in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and their non-epileptic control (NEC) rat strain. Using quantitative and Temporal pattern (T-pattern) analyses, we found that WIN 55,212-2 did not affect the emotional status of GAERS, but it was anxiolytic in NEC. Conversely, WIN 55,212-2 had a sedative effect in GAERS but was ineffective in NEC. Moreover, vehicle-treated GAERS more motivated to explore by implementing more complex and articulated strategies. These behavioral changes correlate with the reduction of 5-HT in the hippocampus and substantia nigra (SN) and noradrenaline (NA) in the entopeduncular nucleus (EPN) in vehicle-treated GAERS compared to NEC rats, which could contribute to their low anxiety status and hypermotility, respectively. On the other hand, the increased level of NA in the EPN and 5-HT in the SN is consistent with an activation of the basal ganglia output-mediated motor suppression observed in WIN 55,212-2-treated GAERS rats. These data support the view of a strain-dependent alteration of the endocannabinoid system in absence epilepsy by adding evidence of a lower emotional responsiveness and a basal ganglia hypersensitivity to cannabinoids in GAERS compared to NEC rats.

Detection of a temporal structure in the rat behavioural response to an aversive stimulation in the emotional object recognition (EOR) task.

Aim of the research was to investigate whether a temporal structure could be detected in the behavioural response to an aversive stimulation. A fear-related memory task was used in rats, placed in a modified version of the Novel Object Recognition task known as Emotional Object Recognition task, i.e. a behavioural assay that orbits around the declarative memory for an aversive experience. To this purpose, twelve male Wistar rats, divided in two groups (Control and Aversive memory), observed after 4 h (OR4h) and after 24 h (OR24h) from the delivery of an aversive stimulation, associated to a specific object, were used. Data were evaluated both in terms of conventional quantitative approaches and by means of T-pattern analysis, namely a multivariate technique able to unveil the temporal structure of behaviour and the relationships amongst the behavioural items in time. Results evidenced several changes between groups and over time as well. Mean occurrences and mean durations showed significant differences between OR4h and OR24h sessions and between Control and Aversive memory groups for behavioural items of Exploration, Object-related aversion and Immobility. T-pattern analysis revealed important changes of behavioural variability, complexity and repetitiveness, (i.e., the three main qualitative features of T-patterns) in the Aversive memory group. These outcomes highlight a simpler and linear behavioural profile, focused only on specific sequences of particularly repetitive events. Overall, the present study demonstrates a) the presence of a temporal organization of fear-related behavioural events and b) the influence of learning on the modifications observed over time.

Effects of Different Anxiety Levels on the Behavioral Patternings Investigated through T-pattern Analysis in Wistar Rats Tested in the Hole-Board Apparatus.

The Hole-Board is an ethologically based tool for investigating the anxiety-related behavior of rats following manipulation of the central anxiety level. The present paper aims to assess behavioral patterning following pharmacological manipulation of emotional assets in Wistar rats tested in this experimental apparatus. For this purpose, the behavior of three groups of rats injected with saline, diazepam or FG7142 was evaluated using conventional quantitative and multivariate T-pattern analyses. The results demonstrate that quantitative analyses of individual components of the behavior, disjointed from the comprehensive behavioral structure, are of narrow utility in the understanding of the subject's emotional condition. Among the components of the behavioral repertoire in rodents tested in the Hole-Board, Edge-Sniff and Head-Dip represent the most significant ones to rate anxiety level. They are characterized by a strong bivariate relationship and are also firmly part of the behavioral architecture, as revealed by the T-pattern analysis (TPA), a multivariate technique able to detect significant relationships among behavioral events over time. Edge-Sniff → Head-Dip sequences, in particular, are greatly influenced by the level of anxiety: barely detectable in control animals, they completely disappear in subjects with a reduced level of anxiety and are present in almost 25% of the total of T-patterns detected in subjects whose anxiety level increased.

The impact of chronic daily nicotine exposure and its overnight withdrawal on the structure of anxiety-related behaviors in rats: Role of the lateral habenula.

Tobacco smoking is a serious health problem worldwide and a leading cause of mortality. Nicotine, the addictive component of tobacco, affects a range of emotional responses, including anxiety-related behaviors. Although perceived by smokers to be anxiolytic, evidence suggests that smoking increases anxiety and that mood fluctuates with nicotine intake. Thus, nicotine addiction may depend on easing the psychobiological distress caused by its abuse. The lateral habenula (LHb) has been implicated as a neural substrate for acute nicotine-induced anxiety, but its role in anxiety-like behaviors associated with chronic nicotine exposure has not been explored. Here, we assessed the effect of chronic nicotine exposure and its subsequent overnight withdrawal on anxiety-like behavior using both quantitative and multivariate T-pattern analysis in rats tested using the hole-board apparatus. Additionally, we explored the role of the LHb by comparing the behavioral effects of short-term nicotine withdrawal in chronically treated LHb-lesioned rats. Quantitative analysis revealed increased anxiety-like behavior in chronically treated overnight nicotine-deprived rats, as manifested in reduced general and focused exploratory behaviors, which was eased in animals that received nicotine. Quantitative analysis failed to reveal a role of the LHb in overnight nicotine deprivation-induced anxiety. Conversely, T-pattern analysis of behavioral outcomes revealed that chronic nicotine-treated rats still show anxiety-like behavior following nicotine challenge. Moreover, it demonstrated that the LHb lesion induced a stronger anxiolytic-like response to the acute challenge of nicotine in chronically nicotine-exposed animals, implicating the LHb in the anxiogenic effect of chronic nicotine exposure. These data further highlight the LHb as a promising target for smoking cessation therapies and support the importance of T-pattern analysis for behavioral analysis.

Recurring sequences of multimodal non-verbal and verbal communication during a human psycho-social stress test: A temporal pattern analysis.

BACKGROUND: The Trier Social Stress Test (TSST) is a widely used protocol to study human psycho-social stress responses. Quantitative reports of non-verbal behaviors have been carried out by means of the Ethological Coding System for Interviews (ECSI). However, no data have described whether and how non-verbal and verbal behaviors take part in the composition of multimodal sequences of communication during the test. METHOD: Five non-verbal ECSI categories and four verbal behaviors related with communication were included in the Ethogram. A focal sampling was employed to ensure a high temporal resolution of the behavioral annotation. T-Pattern Analysis was employed to detect statistically-grounded behavioral sequences. RESULTS: As a first step, frequency, overall duration and mean time length were reported for each component of the Ethogram. Besides, T-Pattern Analysis revealed that communication during TSST is organized according to a complex temporal patterning. We found 51 different sequences (T-patterns): 8 T-patterns included exclusively non-verbal behaviors; 17 T-patterns included verbal behaviors and 26 T-patterns encompassed mixed non-verbal and verbal behaviors. T-patterns were discussed depending on their putative functional meaning since non-verbal behaviors almost did not overlap within patterns. CONCLUSIONS: The implementation of an Ethogram including non-verbal and verbal components highlights the multimodal human communication in TSST. T-Pattern Analysis unveils the real-time interplay among these components. In this study results are discussed according to Jakobson's six constitutive factors of communication.

Early alterations of the behavioural structure of mice affected by Duchenne muscular dystrophy and tested in open-field.

Present study has been carried out to assess whether early alterations of the behavioural structure may be detected in mice affected by Duchenne muscular dystrophy (DMD). To this purpose, both quantitative and T-pattern analysis (TPA) were used to analyse the behaviour of two groups of male, two months old mice, 18 MDX and 18 normal as control, tested in an open-field apparatus. T-pattern analysis is a multivariate technique able to reveal hidden structural features of behaviour and, in particular, its temporal characteristics. As to quantitative analyses, mean durations evidenced a significant increase of Walking, Modified Climbing and Rearing and a significant reduction of Immobile-Sniffing, Paw Licking and Immobility in MDX animals. A similar outcome was present in mean occurrences where the only difference was a significant result in Climbing rather than Immobile Sniffing. In addition, mean occurrences, evaluated for all the behavioural components, showed a significant increase for MDX mice. As to TPA, control mice performed 78 different T-patterns occurring 9500 times, whereas in MDX group 47 different T-patterns occurring 7082 times. Overall, MDX mice showed T-patterns of significantly shorter length. Finally, percent distribution of T-patterns encompassing each component of the behavioural repertoire showed significant differences between Control and MDX groups in all the behavioural components, except Climbing. Results suggest that the combined use of quantitative and temporal pattern analyses offers a useful approach to deeply investigate from a behavioural point of view pre-symptomatic stages of DMD in humans and related animal models as well.

Impulsivity and physical activity: A T-Pattern detection of motor behavior profiles.

The relation between impulsivity and physical activity has been scantly investigated. Actually, during physical activity, several goals are achieved on the basis of a certain dose of impulsiveness. This study detects motor and interactive behavior profiles from athletes with traits of impulsiveness, moderate impulsiveness and non-impulsiveness, performing open motor tasks concerning material, space and interaction behaviors. A specific test was administered to assess the impulsivity profiles of athletes; then the Observational System of Motor Skills, Space, Time and Interaction (OSMOSTI), was used to observe and detect movement sequences patterns throughout T-Pattern detection and analysis (TPA). Recent researches have shown that TPA is a suitable approach to study physical activity in different contexts related, for instance, to sport, dance or exergames. Results of TPA revealed that open motor situations enhance motor behavior profiles especially by comparing participants with different impulsiveness. T-Patterns of non-impulsiveness and moderate impulsiveness traits emphasized much more the executive functions of response inhibition, working memory and mental shifting. In this study we pointed out on how impulsiveness, as a candent trait, traditionally considered that leads to a precipitation, unplanned and risky actions could enhance adequate responses to goal achievements if we consider it far to be a disorder on sport and similar subjects. The tool OSMOSTI and TPA used to observe diverse degrees of impulsivity have evidenced objectively the aim of the study.

Effects of chronic nicotine on the temporal structure of anxiety-related behavior in rats tested in hole-board.

The present study aimed to assess the behavioral effects of chronic treatments of different doses of nicotine by using both quantitative and multivariate T-pattern analysis (TPA), which can reveal hidden behavioral structures, in Sprague-Dawley rats tested in the hole-board apparatus. To this purpose, nicotine ditartrate was administered at the doses of 0.1, 0.5 and 1 mg/kg i.p., three times per day, for 14 consecutive days. As to quantitative evaluations, we observed significant reductions in the mean durations and mean frequencies of walking, climbing, immobile-sniffing and rearing in comparison to control. A significant reduction of edge-sniff and head-dip mean frequencies was also detected for all the doses tested. TPA revealed an increase in the number and the mean length of different T-patterns induced by the three doses of nicotine. On the other hand, a significant reduction of the mean occurrences of T-patterns was revealed. Overall, our results obtained by using both quantitative and T-pattern analyses indicate that chronic nicotine induces an anxiety condition characterized by a behavioral re-organization orbiting around the two main components of hole exploration, that is, head-dip and edge-sniff. A better understanding of the link between nicotine and anxiety might help to find new therapies for smoking cessation.

T-patterns in the study of movement and behavioral disorders.

Aim of the present review is to offer an outline of the application of T-pattern analysis (TPA) in the study of neurological disorders characterized by anomalies of movement and, more in general, of behavior. TPA is a multivariate technique to detect real time patterns of behavior on the basis of statistically significant constraints among the events in sequence. TPA is particularly suitable to analyse the structure of behavior. The application of TPA to study movement and behavioral disorders is able to offer, with a high level of detail, hidden characteristics of behavior otherwise impossible to detect. For its intrinsic features, TPA is completely different not only from quantitative evaluations of behavior such as assessments of frequencies, durations, percent distributions etc. of individual behavioral components, but also from the largest extent of multivariate approaches based, for instance, on the analysis of transition matrices. Various applications of TPA in the study of behavior in human patients and in animal models of neurological disorders are discussed. TPA is a suitable tool to study the movement and behavioral disorders. This review represents a useful background for researchers, therapists, physicians etc. who intend to use this technique.

Different Representation Procedures Originated from Multivariate Temporal Pattern Analysis of the Behavioral Response to Pain in Wistar Rats Tested in a Hot-Plate under Morphine.

Temporal pattern analysis is an advanced multivariate technique able to investigate the structure of behavior by unveiling the existence of statistically significant constraints among the interval length separating events in sequence. If on the one hand, such an approach allows investigating the behavioral response to pain in its most intimate and inner features, on the other hand, due to the meaning of the studies on pain, it is of relevant importance that the results utilize intuitive and easily comprehensible ways of representation. The aim of this paper is to show various procedures useful to represent the results originating from the multivariate T-pattern analysis of the behavioral response to pain in Wistar rats tested in a hot-plate and IP injected morphine or saline as a control.

Combining Quantitative and Qualitative Data in the Study of Feeding Behavior in Male Wistar Rats.

The first step in a behavioral study is represented by the organization of a suitable ethogram, that is, a formal description of individual components of the behavior. Then, each component of such a behavioral repertoire can be quantified (e.g., how many times it occurs, its duration, percent distribution, latency, etc.). However, it is our contention that the possibility to describe the behavior of a living being by means of hundreds or even thousands of numbers concerning isolated components, disjointed from the comprehensive behavioral architecture, does not imply the possibility to use those numbers to reconstruct the meaning of behavior. Such a level of comprehension requires a qualitative approach based on the analysis of behavioral structure and its underlying dynamics. By means of synergic utilization of quantitative and qualitative data a more complete description of a given behavior becomes available. In present study we discuss results obtained from observations of feeding behavior in two groups of male Wistar rats: a control group, under standard diet, and a second group, under hyperglycidic one. Results have been presented both in terms of quantitative evaluations and in terms of structural/qualitative ones, the latter obtained by means of T-pattern detection and analysis. As to quantitative results, mean durations showed a significant reduction of Walking and Feeding and an increase of Hind-Paw Licking and Body Grooming; concerning mean occurrences, a significant increase of Front-Paw Licking, Hind-Paw Licking, and Body Grooming was present; percent distributions showed significant reductions for Walking and Feeding and a significant increase for all grooming activities. As to qualitative assessments, T-pattern analysis unveiled a clear-cut behavioral reorganization induced by the hyperglycidic diet. If on the one hand, 50 different T-patterns were detected in subjects under standard diet, on the other hand, 703 different T-patterns were discovered in animals under hyperglycidic treatment, with a highly significant increase of mean lengths and a significant reduction of mean occurrences of T-patterns. Synergic evaluation of results in terms of quantitative and qualitative aspects shows, in rats fed with hyperglycidic diet, an increased anxiety condition, likely dependent on food-related stimuli and suggestive of a pervasive craving-related behavior.

Effects of Substantia Nigra pars compacta lesion on the behavioral sequencing in the 6-OHDA model of Parkinson's disease.

The basal ganglia circuitry plays a crucial role in the sequential organization of behavior. Here we studied the behavioral structure of the animals after 21 days of 6-OHDA-induced lesion of the dopaminergic nigrostriatal system. Frequencies and durations of individual components of the behavioral repertoire were calculated; moreover, whether a temporal organization of the activity was present, it was investigated by using T-pattern analysis, a multivariate approach able to detect the real-time sequential organization of behavior. Six sham-depleted and six rats with unilateral 6-OHDA-lesion of the Substantia Nigra pars compacta were used. As to quantitative evaluations, the comparison between lesioned and unlesioned rats revealed significant differences only for the mean occurrences of Walking, Immobile Sniffing and Stretched Sniffing, reduced in lesioned subjects. All the remaining components of the behavior did not show significant changes. On the other hand, results from T-pattern analysis showed a reduction of the number of different T-patterns, of their mean length and of their occurrences in 6-OHDA-lesioned rats. Overall, these results suggest that the main deficit in 6-OHDA-lesioned subjects, rather than in the production of individual behavioral components, lies in deficiencies of their sequential organization.

Behavioral fragmentation in the D1CT-7 mouse model of Tourette's syndrome.

AIM: The transgenic D1CT-7 mouse is one of the best-characterized animal models of Tourette's syndrome (TS), exhibiting spontaneous tic-like Head-Body Twitches (HBT) and deficits in sensorimotor gating. This study is aimed at evaluating the behavioral dynamics of these mutants and their potential relevance to TS. METHODS: The behavior of D1CT-7 and Wild Type littermates was firstly assessed by considering frequencies and durations. To detect recurrent real-time behavioral sequences, the multivariate T-pattern analysis was employed. Analyses of transition probabilities among behaviors further provided an overall picture of the behavioral dynamics. RESULTS: T-patterns and transition matrices revealed in D1CT-7 mice a clear-cut hyperactivity compared to controls, with a lower behavioral organization and a marked shift from cautious sniffing toward locomotion. Moreover, the behavioral patterns of the transgenic mice were pervasively disturbed by intrusive tic-like HBT leading to a marked fragmentation of the behavior. Novel exposure to open field provoked a transient inhibitory control over the disrupting phenotype. CONCLUSION: The results of this study show that the D1CT-7 mouse model is subjected to a behavioral fragmentation, with repercussions going beyond the simple tic-like phenomenon. These phenotypes are strikingly akin to behavioral problems observed in patients with TS and further validate the power of this model in summarizing pivotal behavioral aspects of TS.

Brain histamine depletion enhances the behavioural sequences complexity of mice tested in the open-field: Partial reversal effect of the dopamine D2/D3 antagonist sulpiride.

Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.v. injections of alpha-fluoromethylhistidine, a blocker of histidine decarboxylase, on the temporal organization of motor sequences of CD1 mice behaviour in the open-field test. An ethogram encompassing 9 behavioural components was employed. Durations and frequencies were only slightly affected by treatments. However, as revealed by multivariate t-pattern analysis, histamine depletion was associated with a striking increase in the number of behavioural patterns. We found 42 patterns of different composition occurring, on average, 520.90 ± 50.23 times per mouse in the histamine depleted (HD) group, whereas controls showed 12 different patterns occurring on average 223.30 ± 20.64 times. Exploratory and grooming behaviours clustered separately, and the increased pattern complexity involved exclusively exploratory patterns. To test the hypothesis of a histamine-dopamine interplay on behavioural pattern phenotype, non-sedative doses of the D2/D3 antagonist sulpiride (12.5-25-50 mg/kg) were additionally administered to different groups of HD mice. Sulpiride counterbalanced the enhancement of exploratory patterns of different composition, but it did not affect the mean number of patterns at none of the doses used. Our results provide new insights on the role of histamine on repetitive behavioural sequences of freely moving mice. Histamine deficiency is correlated with a general enhancement of pattern complexity. This study supports a putative involvement of histamine in the pathophysiology of tics and related disorders.