Obsessive-compulsive disorder: a disorder of pessimal (non-functional) motor behavior.

OBJECTIVE: To determine whether in addition to repetitiveness, the motor rituals of patients with obsessive-compulsive disorder (OCD) involve reduced functionality due to numerous and measurable acts that are irrelevant and unnecessary for task completion. METHOD: Comparing motor rituals of OCD patients with behavior of non-patient control individuals who were instructed to perform the same motor task. RESULTS: Obsessive-compulsive disorder behavior comprises abundant acts that were not performed by the controls. These acts seem unnecessary or even irrelevant for the task that the patients were performing, and therefore are termed 'non-functional'. Non-functional acts comprise some 60% of OCD motor behavior. Moreover, OCD behavior consists of short chains of functional acts bounded by long chains of non-functional acts. CONCLUSION: The abundance of irrelevant or unnecessary acts in OCD motor rituals represents reduced functionality in terms of task completion, typifying OCD rituals as pessimal behavior (antonym of optimal behavior).

Compulsive checking behavior of quinpirole-sensitized rats as an animal model of Obsessive-Compulsive Disorder(OCD): form and control.

BACKGROUND: A previous report showed that the open field behavior of rats sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria for compulsive checking behavior. In an effort to extend the parallel between the drug-induced phenomenon and human obsessive-compulsive disorder (OCD), the present study investigated whether the checking behavior of quinpirole rats is subject to interruption, which is an attribute characteristic of OCD compulsions. For this purpose, the rat's home-cage was placed into the open field at the beginning or the middle of a 2-hr test. RESULTS: Introduction of the home-cage reduced checking behavior, as rats stayed inside the cage. After 40 min, checking resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had no such effects on quinpirole rats or saline controls. CONCLUSIONS: Checking behavior induced by quinpirole is not irrepressible but can be suspended. Results strengthen the quinpirole preparation as an animal model of OCD compulsive checking.

The morphogenesis of motor rituals in rats treated chronically with the dopamine agonist quinpirole.

Rats injected repeatedly with the dopamine agonist quinpirole develop motor rituals that evolve through a cascade of 4 behavioral processes. The 1st involves increased activity. The 2nd involves increased path stereotypy, reflected in traveling repeatedly along the same few paths. The 3rd is an increase in the frequency of stopping in a few places, along with a decrease in stopping in other places. The 4th is a decrease in the repetition of movements performed in the specific stopping places. Altogether, these processes culminate in stereotypy, a typical short set of movements composed of a single performance of each movement type. Thus, stereotypy arises from changes in the temporal and spatial organization, but not the content, of behavioral patterns. These results provide a model for the development of motor rituals and their linkage to normal behavior and to the physical properties of the environment.

Differential behavioural and hormonal responses of voles and spiny mice to owl calls.

Rodents usually respond to the presence of owls by reducing overall activity, in particular foraging. In this study, a playback of recorded tawny owl, Strix aluco, calls was sufficient to induce a marked effect in the social (Gunther's) vole, Microtus socialis. Some of the voles exposed to owl calls reduced their activity ('freeze' pattern) unlike control voles exposed to a human voice. Other voles, however, dashed around the cage ('flee' pattern). Owl calls also increased corticosterone levels in the voles, showing that the calls induced stress. We suggest that the behavioural dichotomy to freeze or flee in voles is a result of differences in individual normal behaviour and/or in stimulus interpretation. In the common spiny mouse, Acomys cahirinus, no behavioural changes were detected after exposure to owl calls, despite increased cortisol levels which are indicative of stress. Differences in the habitats of voles and spiny mice may explain the apparent lack of behavioural response in the latter. They are rock-dwelling rodents preferentially foraging between boulders and in rock crevices, where they are relatively protected from aerial predation, whereas voles forage in relatively open spaces. Copyright 1999 The Association for the Study of Animal Behaviour.

Role of dopamine systems in obsessive-compulsive disorder (OCD): implications from a novel psychostimulant-induced animal model.

OCD was once considered a rare psychiatric disorder, but recent studies estimate that, in the general population, the lifetime prevalence of OCD is 1 to 2%, twice that of schizophrenia or panic disorder. The most common form of OCD is compulsive checking. Our studies show that the behavior of rats treated chronically with the dopamine agonist, quinpirole, meets the ethological criteria of compulsive checking in OCD; may have a similar motivational basis as compulsive checking in the human; and is partially attenuated by the anti-OCD drug, clomipramine. Thus, the behavioral changes induced by chronic treatment with quinpirole may constitute an animal model of OCD checking. Since behavioral sensitization is an associated effect of quinpirole treatment, the induction of compulsive checking by quinpirole may involve the same mechanisms as the induction of drug-induced sensitization. In this respect, we demonstrated that the MAO inhibitor clorgyline, not only prevented the development of locomotor sensitization to quinpirole, but also reversed it in sensitized rats. To the extent that the quinpirole treatment is an animal model of OCD with strong face validity, it strengthens the hypothesis that dopamine systems play a role in OCD and raises the possibility that MAO inhibitors, which are used clinically for OCD, may exert their effects by acting at the MAO inhibitor displaceable quinpirole binding site.

How the neonatal rat gets to the nipple. II. Changes during development.

In the course of postnatal development, the motor sequence executed by pups in order to attach to the dam's nipple undergoes extensive changes. During the 1st postnatal week, the pup performs a rotation along the longitudinal axis of its trunk to achieve a supine posture under the mother. The pup then crawls on the maternal ventrum while in the supine posture, searching for, finding, and attaching to a nipple. During the 2nd postnatal week, this sequence is modified and the pup first searches and establishes contact with a nipple before rotating to the supine posture. This sequence of movements is then truncated. By postnatal Day 11, pups may attach to a nipple while in a prone posture. Developmental changes in supination before attaching to the nipple are reminiscent of changes in righting during a similar period of development. These observations support the idea that both righting and postural adjustments involved in attachment to the nipple derive from common motor modules, with righting executed in the direction of gravity and rotation to the nipple executed against the force of gravity. The parallel structure of these behaviors is consistent with a common origin and similar control mechanisms for these distinct motor behaviors that are expressed early in postnatal development.

Histology and enzymatic activity in the postnatal development of limb muscles in rodents.

The present work examines how increases in spontaneous motor capabilities during postnatal development are reflected in enzymatic activity and the histology of hindlimb muscles of the dormouse (Eliomys melanurus), the jird (Meriones tristrami), the vole (Microtus socialis), and the spiny mouse (Acomys cahirinus). The precocial neonate of the spiny mouse had the most advanced developmental state of young myofibers with striations as early as 1 week after delivery. At the same age, the altricial neonate vole had less developed muscles compared to the spiny mouse, but was more mature compared to other altricial species. The dormouse was the least developed, with numerous myoblasts and few myotubes at 1 week after delivery. These differences in myogenic development were conspicuous throughout postnatal development. Similar differences between the species were also evident at the biochemical level, as measured in the kinetics of activity of the enzyme creatine-phosphokinase immediately after delivery. On postnatal day 7, the creatine-phosphokinase level in the spiny mouse was fourfold higher than in the dormouse or vole. The enzymatic activity of acid phosphatase decreased during the first week postdelivery in the spiny mouse while peaking in the first, second, and third week in the jird, vole, and dormouse, respectively. These results support the notion that precocial species undergo certain developmental stages in utero, whereas, the same stages commence in altricials only postnatally. For the tested altricial species, the results illustrate that limb muscles in the vole, which displays more basic gaits, mature before limb muscles of the jird and dormouse, which display more specialized gaits.

How the neonatal rat gets to the nipple: common motor modules and their involvement in the expression of early motor behavior.

One-day-old rat pups adopt a supine posture before attaching to the mother's nipple. Body rotations performed to reach the nipple occur in a typical kinematic structure. First, the pup rotates along the longitudinal axis of the trunk and lies on its side. Next, the pup arches the trunk to achieve a U-shaped posture and then rapidly relaxes the trunk. A second cephalocaudal rotation follows at the peak of trunk relaxation as the pup achieves a supine posture. After reaching a supine posture, the pup crawls to a nipple by performing "stepping" movements on the mother's ventral surface. The kinematic structure of these movements is reminiscent of the structure of righting as seen in the newborn rat. Both righting and achieving a supine posture under the mother involve the expression of common motor modules. During righting the modules are executed in the direction of gravity, and when achieving a supine posture the modules are executed against the force of gravity. Simple motor behaviors expressed by the rat pup during early postnatal development may have common origins and common control mechanisms.

Quinpirole induces compulsive checking behavior in rats: a potential animal model of obsessive-compulsive disorder (OCD).

Rats treated chronically with the dopamine agonist quinpirole (0.5 mg/kg, twice weekly x 10) met 5 criteria for performance of compulsive checking. Specifically, in a large open-field with single small objects in 4 of 25 locales, quinpirole rats revisited two places/objects excessively often and rapidly, compared with other locations in the environment or saline controls. They performed a ritual-like set of behavioral acts at these two places/objects and stopped in relatively few locales before returning to the preferred places/objects. Finally, they shifted their behavior to a new location when the object was moved there. Clomipramine (10 mg/kg, daily) postponed but did not prevent the development of the quinpirole effect. Quinpirole-induced compulsive checking may be an exaggeration of normal checking of home site in rats. Results suggest an animal model of obsessive-compulsive disorder and a role for dopamine in this disorder.

Effects of diazepam and buspirone on the behaviour of wild voles (Microtus socialis) in two models of anxiety.

Exploration models of anxiety rely almost universally on the use of laboratory species. Furthermore, the spontaneous patterns of locomotion displayed are often interpreted as being an expression of antipredator defense. However, there is no direct link between the experience of these animals and the proposed motivation for their behaviour. To address this problem, the behaviour of wild trapped voles (Microtus socialis), a small-rodent species that is heavily predated upon, was examined in the elevated plus-maze and the black/white exploration model. It was hypothesised that the patterns of locomotion in these exploration models of anxiety should be similar to those reported for laboratory animals if the reactions of the laboratory animals are related to antipredator defense. Data revealed that voles show a similar preference for the protected areas in these models (closed arms or dark section) and that this preference can be modified by buspirone and diazepam. Interestingly, although the effective doses of each drug was the same within each model, it differed between models, with the minimum effective doses of these compounds being lower in the black/white exploration model (1 mg/kg) than in the elevated plus-maze (4 mg/kg). These data provide valuable information concerning the actions of anxiolytic compounds in wild trapped animals as assessed by formal laboratory models and provide useful verification that findings in these models may be generalised to species other than laboratory rodents.

The developmental order of bipedal locomotion in the jerboa (Jaculus orientalis): pivoting, creeping, quadrupedalism, and bipedalism.

This is a brief report on the postnatal development of locomotor behavior in the jerboa, a bipedal kangaroo-like rodent. Observations on one litter revealed three intriguing aspects of the postnatal development of the jerboa compared to other rodent species: (a) The weaning period is extended, (b) the developmental stage in which pivoting is the main locomotor activity is extended, and (c) locomotor performance is differently related to anatomical growth. Jerboa pups are born after a long pregnancy compared to other altricial rodents, but possess typical neonate morphology: The hindlegs and forelegs are of the same length, the tail is short, skin pigmentation and fur are absent, and the eyes and ears are closed. However, the neonate jerboa differs from other rodents in posture and activity: Its hindlegs extend laterally to the same side of the pelvis and it creeps with stepping of only the forelegs that drag the trunk while the hindlegs remain passive. Pivoting and creeping are preserved in the jerboa for 4 weeks, as compared to a few days in other species. Afterwords, quadruped locomotion emerges and the jerboa pup walks while folding its long hindlegs to the same functional length as the forelegs. Bipedal locomotion is acquired only in postnatal Day 47. These observations illustrate that further studies of the development of the jerboa, as well as other bipedal rodent species, may provide new perspectives on anatomy, histology, physiology, and motor behavior during postnatal development.

Postnatal development of body architecture and gait in several rodent species.

Observations on five species of rodents, vole (Microtus socialis), gerbil (Gerbillus dasyurus), jird (Meriones tristrami), dormouse (Eliomys melanurus) and jerboa (Jaculus orientalis), revealed that, during the period when their neonates share a matching morphology, they also share the same forms of quadruped locomotion (gaits). The order in which the different gaits develop is similar in all species, beginning with the basic gaits of lateral walk and trot. Gaits and body morphology do not undergo further changes in voles, whereas the other species incorporate more specialized gaits later in ontogeny, when the adult body morphology has been attained. Gerbils and jirds incorporate a bounding gait, dormice incorporate galloping and jerboas incorporate bipedal running. Species with more specialized locomotion thus undergo more developmental stages than those with less specialized locomotion. Except for the jerboa, the nesting period was roughly the same for all species, but those with more specialized locomotion exhibited earlier onset of the basic gaits as if condensing their development in order to reach the adult gait within the same nesting period. Consequently, the adult gait emerges approximately 10 days before the end of nesting, regardless of nesting duration. Since growth rate does not seem to account for the differences in morphology and onset of gaits, the heterochrony in the observed species probably stems from differences in the duration of growth, which seems to be the key factor in the diversion from the basic common morphology. The present results reconfirm the traditional generalities of functional morphology derived from cross-species comparisons. In addition, they provide another perspective by comparing form and function within the same individuals in the course of ontogeny.

Animal model and in vitro studies of anti neurofilament antibodies mediated neurodegeneration in Alzheimer's disease.

Alzheimer's disease (AD) is associated with serum antibodies directed specifically against phosphorylated epitopes highly enriched in the heavy neurofilament protein NF-H of cholinergic neurons. Prolonged immunization of rats with these molecules but not with other NF-H isoforms results in cognitive impairments. This animal model, termed experimental autoimmune dementia (EAD), supports a role for such antibodies in neurodegeneration in AD. In the present study we investigated the cellular and immunological mechanisms underlying the cognitive defects in EAD. Immunohistochemical studies revealed that IgG accumulate in the septum, hippocampus and in the entorhinal cortex of the EAD rats. This is accompanied by a marked reduction in the density of septal cholinergic neurons. An inverse correlation was observed between the level of IgG in the septum of individual EAD rats and the density of their septal cholinergic neurons. Time course studies revealed that the decrease in the density of cholinergic neurons in the septum of EAD rats and the accumulation of IgG in this brain area have the same time course and are both significant by three to four months following the initiation of immunization with cholinergic NF-H. The cognitive deficits of the EAD rats evolve more slowly and are pronounced only after six months following the initation of immunization. In vitro studies revealed that anti NF-H IgG bind to the outer surface of neurons in tissue cultures of rat forebrain and can affect neuronal viability. These AD and in vitro findings provide model systems for studying the mechanisms underlying the neuropathological effects of specific anti NF-H antibodies.

Exploration and predation models of anxiety: evidence from laboratory and wild species.

The current article addresses several issues within the context of issues within the context of modeling human anxiety disorders in the laboratory. First, evidence is presented to support the suggestion that behavior in exploration models of anxiety may be motivated by apprehension relating to intraspecific encounters rather than interspecific, predator/prey interactions, which has consequences for the interpretation of findings generated using these tests. Second, data are reviewed concerning the use of stimuli indicating the presence of a predator in the context of anxiety modeling, and it is suggested that tests involving the reactions of animals following exposure to such stimuli may be more closely related to pathologic anxiety mechanisms than tests employing observations during contact with these stimuli. Third, comparative studies, using wild-caught rodents, are outlined that show that, although there are similarities in the defensive strategies adopted by these animals in response to the call of an owl, there are also important differences. Finally, the suggestion is made that the distance-dependent-defense-hierarchy may be of important heuristic value in the interpretation of these data and that, perhaps more significantly, it may also provide a mechanism that allows animal defensive strategies and human anxiety disorders to be placed within the same conceptual framework.

Uphill locomotion in mole rats: a possible advantage of backward locomotion.

Mole rats were videotaped while locomoting in a Plexiglas tube to evaluate the effects of inclination on locomotion. Animals moving uphill preferred to go backward using plantigrade foot postures, presumably to prevent sliding. Uphill backward locomotion also allowed animals to cope with changes in weight distribution between the hind and forelimbs without modifying footfall pattern relative to the direction of progression. When the animals did use uphill forward strides, they switched to asymmetrical gaits, which are associated with increased propulsive forces. These and prior results suggest that weight distribution and direction of progression can modify the natural pattern of stepping in mammalian quadrupeds.

Postnatal development of synchronous stepping in the gerbil (Gerbillus dasyurus).

During the first two postnatal weeks, Wagner's gerbil (Gerbillus dasyurus) pups employed stepping sequences considered to be more basic than in the later stages of development and displayed alternate stepping of the legs in each girdle. In the third postnatal week, the adult mode of locomotion, the bound, became prominent and synchronous stepping dominated locomotion, gradually replacing alternate stepping. Motor performance of the gerbil pups corroborates previous studies in following a developmental motor gestalt termed 'warm-up', which involves an ordered incorporation of movements along three distinct spatial dimensions. In the present results, the validity of warm-up has been extended to a quantitative perspective: the order in which movement types reached their peak performance was identical to the order of their emergence in ontogeny. Transient modes of locomotion were also employed by gerbil pups during postnatal development, in accordance with changes in body morphology, indicating that there exists a causal link between body design and specific modes of locomotion.

Dynamics of behavioral sensitization induced by the dopamine agonist quinpirole and a proposed central energy control mechanism.

The study characterizes the process of sensitization induced by intermittent administrations of quinpirole (0.5 mg/kg) in rats in a large open field. Sensitization was found to be self-limiting, with all measures of behavior reaching a plateau after the tenth twice-weekly injection. Kinetics of sensitization were a simple hyperbolic function of the number of drug injections for some measures (speed of locomotion, length of locomotor bouts) but showed positive co-operativity for others (distance travelled, duration of locomotion, frequency of stops, route stereotypy), suggesting potentiation of the effect by preceding injections. The pace of sensitization varied for different behaviors: locomotor speed changed fastest in the early portion of chronic treatment; stereotypy of route changed primarily during the late phase; mouthing did not sensitize. Sensitization evolved by a cascade of changes that included: advancing the onset of locomotor activation; prolonging the duration of locomotion; establishing new maxima of observable responses; altering the mode of locomotion; raising speed, rate and length of locomotor bouts; and increasing stereotypy of travel. These observations do not substantiate the prediction that development of behavioral sensitization is associated with emergence of disorganized activity and/or fractionation of response chains. Instead, it is proposed that development of sensitization may represent a build-up and strengthening of performance, reflecting enhanced central control of energy expenditure stimulated by repeated injections of quinpirole. Furthermore, it is suggested that for at least one response, the maximum observable amount of locomotion, development of sensitization requires only D2 stimulation, independent of D1 tone.

Influence of body morphology on turning behavior in carnivores.

The present work illustrates how three carnivore species with different body morphologies differ in the performance of a basic motor component-turning. Marbled polecats, which have an elongated and slender trunk, turn while sharply bending the trunk laterally. Grey wolves possess elongated legs and turn by maneuvering with their legs while slightly bending the trunk laterally and lowering the head to contact the ground. Honey badgers feature a wide and massive bear-like shape and rarely bend the trunk, but rather turn either by maneuvering with their legs or while elevating parts of the trunk in the vertical domain. It is suggested that these strategies shorten the radius of turning and thus reduce the moment of inertia. A lower moment of inertia may optimize turning behavior in terms of speed, energy cost, and the smoothness of transition between turning and bouts of forward progression or arrest.

Disintegration of the spatial organization of behavior in experimental autoimmune dementia.

Experimental autoimmune dementia is a rat model designed to examine the potential role of anti-cholinergic neurons antibodies in neuronal degeneration in dementia and Alzheimer's disease. We have previously shown that sera of patients with Alzheimer's disease contain antibodies which bind specifically to the high molecular weight neurofilament protein of the purely cholinergic electromotor neurons of Torpedo. Production of such antibodies in experimental autoimmune dementia rats by prolonged immunization with the Torpedo cholinergic high molecular weight neurofilament subunit results in accumulation of antibodies in the septum and hippocampus of the immunized rats, in a marked decrease in the density of forebrain cholinergic neurons, and in memory deficits. In the present study we characterized the open-field behavior of experimental autoimmune dementia rats, and examined whether, like in dementia, the spatiotemporal organization of their behavior is impaired. The results obtained revealed that experimental autoimmune dementia rats travel shorter distances; explore a smaller part of the open-field; and perform less round-trips to the key location--the home base--in reference to which their behavior is normally organized. The shrinkage of the explored space and the reduced number of round trips are independent of the amount of locomotion and represent a deterioration in the organization of behavior in time and space. These behavioral changes are specific to the anti-cholinergic immune response of experimental autoimmune dementia rats as they are not observed in rats which were immunized with chemically heterogeneous high molecular weight neurofilament subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased density of forebrain cholinergic neurons and disintegration of the spatial organization of behavior in experimental autoimmune dementia (EAD).

Experimental autoimmune dementia (EAD) is a rat model designed to examine the potential role of anti-cholinergic neurons antibodies (Abs) in the neuropathology of Alzheimer's disease (AD) and dementia. We have previously shown that sera of AD and Down's syndrome patients contain Abs which bind specifically to the high molecular weight neurofilament protein (NF-H) of the purely cholinergic electromotor neurons of Torpedo. Production of such Abs in EAD rats by prolonged immunization with Torpedo cholinergic NF-H results in the accumulation of IgG in the septum and hippocampus of the immunized rats and in memory deficits. In the present study, we examined immunohistochemically whether the anti-cholinergic NF-H immune response of the EAD rats affects their brain cholinergic neurons. In addition, since dementia is associated with severe deterioration in the spatio-temporal organization of behavior, we examined whether EAD rats also mimic this important feature of dementia. The results obtained show that production in EAD rats of anti-cholinergic NF-H Abs similar to those found in AD patients results in a marked decrease in the density of forebrain cholinergic neurons and in derangements in the spatio-temporal organization of their behavior. These findings may replicate pathogenic processes in AD and support a role for anti-cholinergic NF-H Abs in the degeneration of cholinergic neurons in the disease.