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H Szechtman

Publications and source records attributed to H Szechtman.

At least 55 records · Page 3Linked to original sources
PubMed1994

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.

Amphetamine↗
PubMed1994

Disturbed emotionality in autoimmune MRL-lpr mice.

MRL-lpr mice develop symptoms of autoimmune lupus-like disease early in the life and MRL(-)+/+ mice develop it substantially later. The present study examines our previous suggestion that autoimmune MRL-lpr mice show altered emotional reactivity. In addition, it aims to identify the set of measures which best discriminate the behavior of MRL-lpr mice from their congenic controls (MRL +/+). Behavior of males from these two substrains (n = 40/substrain; 3-4 mo of age) was compared on a battery of tests presumed to be reflective of emotional reactivity. MRL-lpr mice explored the open field less, spent more time at home-base, and defecated less in comparison to congenic MRL +/+ controls. Moreover, MRL-lpr mice hesitated to step down from an elevated platform and to make contact with a novel object. They also visited open-arms of a plus-maze less often and showed extensive floating in the Porsolt's swim test. Discriminant analysis revealed that the performance of the MRL-lpr and MRL +/+ mice differed most profoundly on measures taken in the Porsolt's swim and step-down tests. In addition, in the MRL-lpr group high titers of serum antinuclear antibodies were associated with impaired exploration of a novel object. These results are consistent with the previously proposed notion of increased "timidity" in autoimmune MRL-lpr mice and of an immune factor contribution to altered emotional reactivity. Considering that behavior of autoimmune MRL-lpr mice resembles behavior of stressed animals, it is speculated that disturbed emotional reactivity reflects the effect of autoimmunity on the hypothalamic-pituitary-adrenal axis.

Animals↗
PubMed1994

Effects of dose and interdose interval on locomotor sensitization to the dopamine agonist quinpirole.

To assess whether the interval between injections affects the course of locomotor sensitization to quinpirole, groups of rats were injected every 2, 4, or 8 days with quinpirole (0, 0.025, 0.25, 0.5, and 2.5 mg/kg; n = 222) and their locomotor activity monitored after each injection for a total of 10 tests. Results indicate that the number of drug injections, rather than the interval between them, predominantly controls the development of locomotor sensitization to quinpirole. It is suggested that this may reflect a rapid induction but slow decay time for a response-enhancing factor stimulated by each injection of quinpirole, and that the effects of this putative factor are cumulative but saturable.

Animals↗
PubMed1993

Role of the corpus callosum in expression of behavioral asymmetries induced by a unilateral dopamine lesion of the substantia nigra in the rat.

The present study examines the effects of sectioning the corpus callosum on the expression of asymmetric behaviors induced by a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantial nigra. Severing the corpus callosum eliminated the asymmetry in spontaneous investigation of edges in an open-field, without affecting total time of investigation. In contrast, callosotomy reduced the magnitude of externally cued turning, but failed to affect the directional distribution of responding. Moreover, it reduced the magnitude of apomorphine- but not amphetamine-induced turning. It is suggested that transcallosal communication is required for those behavioral asymmetries induced by a unilateral dopamine lesion which depend on head, rather than whole body movements.

Amphetamine↗
PubMed1993

Longlasting consequences of chronic treatment with the dopamine agonist quinpirole for the undrugged behavior of rats.

This study asks whether apart from behavioral sensitization, chronic treatment with the D2 dopamine agonist quinpirole produces long-term effects on undrugged behavior. Rats (n = 12) were pretreated with 10 injections of quinpirole (0.5 mg/kg every 4 days in activity cages), producing a 6-fold increase in locomotor activity. Ten days later, their undrugged behavior was assessed in a large open field, and their spatial learning in a Morris water maze; the entire procedure was repeated 3 months later. Control animals were pretreated with saline and tested in the open field either undrugged (n = 12) or with acute quinpirole (n = 12); only undrugged controls were used for spatial learning. Results indicate that quinpirole pretreatment results in persisting changes that can be characterized as a reduction in the rat's freedom of movement. Compared to vehicle controls, quinpirole pretreated rats turn with a more rigid body, show more repetitive travel along the same routes in the open field, and perseverate more during extinction in the water maze. These effects are weaker at 3 months postsensitization. In all other respects (level of activity in the open field and acquisition learning) Sensitized rats behave no differently from vehicle controls. Changes in undrugged behavior in the open field resemble the effects of quinpirole but are smaller in magnitude. It is suggested that the alteration in undrugged behavior reflects compensatory behavioral adaptation to the exaggerated hyperactivity induced by quinpirole.

Animals↗
PubMed1993

Spatial learning during the course of autoimmune disease in MRL mice.

The present study examines whether autoimmune MRL-lpr mice develop impairments in learning and memory that correlate with changing severity of lupus-like disease. MRL-lpr mice (n = 20) were tested in the Morris water-maze at 12, 14, 16 and 18 weeks of age. Age-matched controls were congenic MRL +/+ mice (n = 20) that develop the disease much later. Immune status was assessed by the presence of anti-nuclear antibodies (ANA), brain-reactive antibodies, proteinuria, and haematocrit. Learning rates and memory retention did not differ between the substrains, and did not correlate or deteriorate with advancing age and autoimmunity. However, the baseline performance level in autoimmune MRL-lpr mice was shifted, as evidenced by a consistently longer task-solving latencies. Thigmotaxic swimming (along the pool wall) was pronounced in the MRL-lpr group, and was associated with the observed difference in performance. The present study does not support the notion that learning/memory abilities of autoimmune MRL-lpr mice are impaired per se, but may support the hypothesis that the rapid progress of humoral autoimmunity affects the emotionality of lupus-prone mice.

Animals↗
PubMed1993

Brain-reactive antibodies and behavior of autoimmune MRL-lpr mice.

The hypothesis that brain-reactive autoantibodies (BRA) impair behavior was examined in MRL-lpr mice, which develop spontaneous autoimmune disease. Circulating BRA were measured as in vitro serum reactivity to Neuro-2A neuroblastoma cell line, and behavioral competence was assessed in activity monitors, open field, beam walking, and Morris water maze task. Mice with BRA in serum (BRA positive) exhibited slower spontaneous locomotion in a novel environment, shorter grooming episodes, and less exploration of the open field centre when compared to age-matched 7-11-week-old BRA-negative cagemates. Moreover, when initially exposed to the large swimming pool, BRA-positive mice showed increased swimming along the wall, but had no difficulty in learning the water maze task or in traversing a narrow beam. Brain-reactive autoantibodies titre and behavioral measures were not correlated, suggesting that the concentration of serum BRA is not reflective of the magnitude of behavioral impairment. Nevertheless, the present study suggests that the presence of circulating BRA is associated with impaired exploration and/or enhanced emotional reactivity in MRL-lpr mice. It also supports the hypothesis of a pathogenic role of BRA in various mental disorders.

Animals↗
PubMed1993

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)

Afferent Pathways↗
PubMed1993

Three clinical syndromes of schizophrenia in untreated subjects: relation to brain glucose activity measured by positron emission tomography (PET).

A number of studies of chronically ill, medicated patients have found that the clinical symptoms of schizophrenia segregate into three syndromes which can be labelled poverty, disorganization, and reality distortion. It has been previously found that each of these syndromes is associated with a specific pattern of perfusion (rCBF) in paralimbic and association cortex and in related subcortical nuclei. We replicated the symptom factors in 20 untreated subjects. Utilizing positron emission tomography with 18-F-fluorodeoxyglucose as a tracer for glucose metabolism, we reconstructed a map of the entire cortical activity from 16 to 20 tomographic slices. Each of the three syndromes was associated with a different pattern of regional glucose metabolism. Findings in common with previous studies were an association of poverty with left cortical metabolic activity in prefrontal and superior parietal areas, reality distortion with left temporal activity, and disorganization with left inferior parietal lobule. This is the first report of an association between regional metabolic activity and clinical syndromes in untreated patients, strengthening previous models of distributed neural networks in this disorder.

Adolescent↗
PubMed1992

Quinpirole alters quadruped activity in rats from the second postnatal week.

The present study shows that the effects of quinpirole (1 mg/kg) during the second postnatal week but not before resemble the effect of the drug in adult rats in increasing quadruped activity, eliminating grooming, reducing lateral bending, and stimulating verticalized turning. Quinpirole also modifies the morphology of turning behavior, the primary form of coordinated quadruped locomotion in neonate laboratory rat pups. Under saline, turning involves lateral bending and straightening of the trunk. Under quinpirole, turning includes a vertical component of movement ("verticalized turning") instead of the normal lateral bending of the trunk. A similar trend of change in turning is induced by quinpirole in adult rats: An acute injection reduces lateral bending, and a chronic treatment increases verticalization. The induction of vertical turning in the second but not the first postnatal week may stem from the normal course of development since typical vertical movements of intact rats (supported rearing and wall climbing) develop only by the age of 11-14 postnatal days. Verticalized turning may be thus a drug-induced expression of an age-related tendency to perform vertical movements.

Aging↗
PubMed1992

Dopaminergic control of locomotion, mouthing, snout contact, and grooming: opposing roles of D1 and D2 receptors.

The study compares the behavioral profiles induced in rats (N = 118) by the D2-dopaminergic receptor agonist quinpirole (0.03 and 0.5 mg/kg), and the D1-agonist SKF38393 (1.25-40 mg/kg), and both agonists administered together. Locomotion and snout contact frequency were reduced by the low but increased by the high dose of quinpirole; SKF38393 also reduced these behaviors and attenuated the effect of the high quinpirole dose. Only the high dose of quinpirole increased the duration of snout contact bouts and the frequency of mouthing; SKF38393 had no effect but in combination with the high dose of quinpirole, it enhanced the performance of these behaviors greatly. The duration of mouthing bouts was not affected by either agonist but was greatly extended when SKF38393 was administered together with the high dose of quinpirole. Grooming was inhibited by both the low and the high dose of quinpirole, and stimulated by the injection of SKF38393 or its addition to the low dose of quinpirole. These findings suggest that snout contact is controlled by modulating the frequency of episodes whereas mouthing is controlled by modulating the duration of episodes. Moreover, although they do not disprove the prevailing notion of D1-D2 receptor synergism, the present data are consistent also with an oppositional model of D1-D2 receptor interaction in the regulation of locomotion, snout contact, mouthing, and grooming in intact animals.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Constriction of environmental space and the behavioral response to the dopamine agonist quinpirole.

The present study examines the influence of size of testing environment on the behavioral profile seen following injection of the dopamine D2 receptor agonist quinpirole (0.5 mg/kg, n = 16) or saline (n = 16). All rats were tested in a counterbalanced order in both a small and large environment. Oral (licking) behaviors were observed exclusively in the small environment and only in drug-treated rats; moreover, quinpirole increased rearing in the small but not large environment. Other behaviors--sniffing, face and body grooming--were affected by quinpirole but not in an environment-dependent manner. It is concluded that limiting environmental space promotes emergence of oral responding under quinpirole. The self-directed nature of this licking (paw- and tail-licking) may reflect a hierarchical transformation of quinpirole-induced hyperactivity from exploration of space to investigation of body parts.

Animals↗
PubMed1992

A behavioral profile of autoimmune lupus-prone MRL mice.

Manifestations of the human autoimmune disease systemic lupus erythematosus (SLE) include a number of behavioral and cognitive deficits. The present study asks whether neurobehavioral dysfunction is present also in MRL mice that spontaneously develop most of the fundamental immunological aberrations of SLE. There are two congenic substrains of MRL mice that differ in the time of disease onset: MRL-lpr mice develop lupus early and MRL(-)+/+ develop the typical signs of disease relatively late in life. The behavior of these substrains was assessed at 7 to 11 weeks of age, a time that coincides with the onset of disease in MRL-lpr mice and the absence of known lupus symptoms in the MRL(-)+/+ group. When compared to the congenic MRL(-)+/+ control substrain, MRL-lpr mice were spontaneously less active, traversed a crossbeam slower, and ceased responding to the novelty of a new environment sooner. They were also more reluctant to leave their home base or travel far away from it and perseverated in their response bias during extinction and reversal learning. Immunological status was characterized by moderate proteinuria in both substrains and high titers of antinuclear antibodies in MRL-lpr but not MRL(-)+/+ mice. Histological analysis revealed minimal or no signs of joint pathology in MRL-lpr mice. Thus, this study shows the presence of behavioral dysfunction in mice with early stages of autoimmune disease and gives support for the idea that MRL mice may provide a useful model of neurobehavioral dysfunction in SLE. It is suggested that the behavioral profile of MRL-lpr mice may indicate increased "timidity," related to genetics, autoimmunity, or both.

Animals↗
PubMed1992

Toward a brain map of auditory hallucinations.

OBJECTIVE: This study asks whether auditory hallucinations are reflected in a distinctive metabolic map of the brain. METHOD: Regional brain metabolism was measured by positron emission tomography with [18F]-fluorodeoxyglucose in 12 DSM-III schizophrenic patients who experienced auditory hallucinations during glucose uptake and 10 who did not. All patients were free of neuroleptics and 19 had never been treated with neuroleptics. Nine patients were reexamined after 1 year to assess effects of neuroleptic treatment. RESULTS: Compared with the patients who did not experience hallucinations, the patients who did experience hallucinations had significantly lower relative metabolism in auditory and Wernicke's regions and a trend toward higher metabolism in the right hemisphere homologue of Broca's region. Hallucination scores correlated positively and significantly with relative metabolism in the striatum and anterior cingulate regions. Neuroleptic treatment resulted in a significant increase in striatal metabolism and a reduced frontal-parietal ratio, which was significantly correlated with a decrease in hallucination scores. CONCLUSIONS: Auditory hallucinations involve language regions of the cortex in a pattern similar to that seen in normal subjects listening to their own voices but different in that left prefrontal regions are not activated. The striatum plays a critical role in auditory hallucinations.

Adult↗
PubMed1991

Differential effects of D1 and D2 dopamine agonists on stereotyped locomotion in rats.

The study examines the effect of selective D1 dopamine stimulation with SKF38393 (1.25-10 mg/kg), on stereotyped locomotion induced by the D2 agonist, quinpirole (0.5 mg/kg). Quinpirole induces repeated travel along a few routes in a limited portion of the environment. Co-administration of low doses of SKF38393 (1.25-2.5 mg/kg) produces the following results: the rate of route perseveration is not affected; the area explored expands to encompass the entire periphery of the open field; and, spatial distribution of locomotion is transformed from routes that cross the center under quinpirole to travel only along the edge. Under higher doses of SKF38393, locomotion ceases. These findings suggest that D1 and D2 stimulation may control the spatial organization of locomotion in oppositional rather than synergistic manner.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Apomorphine effects on brain metabolism in neuroleptic-naive schizophrenic patients.

Since neuroleptic treatment produces a significant increase in striatal metabolism relative to cortical metabolism, we wished to determine whether the dopamine agonist apomorphine (APO) might have the opposite effect, and whether it would discriminate schizophrenic patients from healthy controls. Eleven neuroleptic-naive schizophrenic patients (diagnosed according to DSM-III) and eight normal subjects were compared with respect to cerebral accumulation of 18F-fluorodeoxyglucose measured by positron emission tomography following APO, 0.75 mg/70 kg (weight adjusted), or saline. Relative striatal glucose metabolism decreased significantly after APO in schizophrenic patients but not in control subjects. Post hoc analysis of data in 12 other regions revealed that relative superior temporal metabolism decreased very slightly, but significantly, in schizophrenic patients but not in control subjects after APO, and that the posterior frontal region increased in control subjects but not in the patient group.

Adolescent↗
PubMed1991

Substance abuse and schizophrenia: effect on symptoms but not on neurocognitive function.

The authors compare symptoms and neuropsychological test performance in DSM-III schizophrenic patients who reported prior substance abuse (N = 38) with those in patients who reported no such abuse (N = 25) to determine the impact of substance abuse on the psychopathology of schizophrenia. Positive and negative symptom scores were derived from the Schedule for Affective Disorders and Schizophrenia. Sixty neuropsychological measures drawn from commonly used tests of intelligence, memory, learning, fluency, and problem solving were calculated. Separate analyses were performed on patients in a psychotic episode who were free of neuroleptics (N = 27) and on those taking maintenance neuroleptics (N = 36). Among unmedicated patients, those who reported prior substance abuse had significantly higher thought disorder scores. Among neuroleptic-medicated patients, hallucination and delusion scores were significantly higher in the patients who reported prior substance abuse. The substance abuse followed withdrawal from social relations and preceded the onset of positive symptoms. None of the neuropsychological tests discriminated between abusers and nonabusers.

Adult↗