Biomedical subjects

W J Kernan

Publications and source records attributed to W J Kernan.

13 recordsLinked to original sources

PubMed1992

Effects of yohimbine and idazoxan on motor behaviors in male rats.

Yohimbine, an alpha 2 adrenergic antagonist, facilitates copulatory behaviors in male rats. This facilitation may reflect nonspecific activation of behavior rather than a more selective activation of copulatory behaviors. The present experiments assessed the effects of yohimbine on locomotor behaviors at a dose (2.0 mg/kg) known to facilitate sexual behaviors. Experiment 1 used a computer pattern-recognition system to classify motor behaviors into specific acts and act groups. Male albino rats were tested in three conspecific conditions: estrous female, anestrous female, or no conspecific. Yohimbine decreased locomotor activity in all three conspecific conditions. Experiment 2 examined the effects of yohimbine (2.0 mg/kg) and amphetamine (1.0 mg/kg) on locomotor behavior in a photocell-equipped activity measurement system. Amphetamine increased and yohimbine decreased locomotor activity. Experiment 3 used the computer pattern-recognition system to compare the effects of yohimbine and idazoxan, another alpha 2 adrenergic antagonist, on motor behaviors. Yohimbine and idazoxan both decreased activity but produced different patterns of behavioral change. The facilitatory effects of yohimbine on copulatory behaviors at a dose of 2.0 mg/kg are apparently not mediated by nonspecific activation of behavior.

Adrenergic alpha-Antagonists↗

PubMed1992

Reproducibility of time structure in motor activity of rats under nocturnal conditions.

Computer pattern recognition systems for the study of spontaneous rat behavior have introduced a new analytical technique, the K functions, that expands the definition of experimentally induced changes in behavior. Such studies normally evaluate three measures, a measure of the number of initiations of specific behavioral acts, a measure of the total time of each act, and a measure of behavioral time structure, the K functions. Such measures have been shown to be very stable and reproducible among control rats observed under normal light conditions. This study examines the stability of results from these three measures as applied to nine different groups of control Sprague-Dawley male rats observed under red light during their normal nocturnal hours. All three measures provided stable and reproducible results, but the measure of time structure, the K function analysis, provided the greatest consistency, producing values that vary by only a few percent.

Adrenergic alpha-Antagonists↗

PubMed1992

A statistical test to assess changes in spontaneous behavior of rats observed with a computer pattern recognition system.

A computer pattern recognition system, RAPID, has been used to study the spontaneous motor activity of Sprague-Dawley rats. This system produces a large number of measures of the activity of control and experimental groups in any given study. The large number of measures involved presents a problem when one attempts to decide whether the behavioral activity of the exposed group differs from that of the control group. Extensive Monte Carlo studies have been performed in an attempt to develop and validate a simple statistic to be used in such decisions.

Animals↗

PubMed1991

Stability and reproducibility of time structure in spontaneous behavior of male rats.

The computer pattern recognition system for the study of spontaneous rat behavior has allowed new analytical techniques which expand the definition of experimentally induced changes in behavior. As with any technique, the stability of the measures must be considered when evaluating overall sensitivity. This study evaluates the stability and reproducibility of three behavioral measures: a measure of the number of initiations of specific behavioral acts, a measure of the total time of each act, and a measure of behavioral time structure. Normal statistical parameters are used to evaluate the significance of changes detected using the first two measures, but the third measure utilizes K-functions, the bootstrap and ad hoc criteria to evaluate significance of observed changes. This study compares the stability of results from these three measures as applied to fourteen different groups of control Sprague-Dawley male rats. All three measures provided stable and reproducible results, but the measure of time structure, the K-function analysis, provided the greatest consistency. Behavior, particularly spontaneous behavior, has traditionally been perceived as being intrinsically variable. However, this study shows that the computer pattern recognition system and its analytical techniques provide stable and reproducible values that vary only a few percent.

Amphetamine↗

PubMed1991

No change in spontaneous behavior of rats after acute oral doses of aspartame, phenylalanine, and tyrosine.

Spontaneous behavior subsequent to acute oral administration of high doses of aspartame, phenylalanine, or tyrosine was analyzed using a computer pattern recognition system. Sprague-Dawley male rats (250-300 g) were dosed orally with aspartame (500 or 1000 mg/kg), phenylalanine (281 or 562 mg/kg), or tyrosine (309 or 618 mg/kg), and their behavior was analyzed 1 hr after dosing. The computer pattern recognition system recorded and classified 13 different behavioral acts performed by the animals during the first 15-min exploration of a novel environment. Three measures that provide independent information concerning motor output from the central nervous system were taken: the number of behavioral initiations, total time, and time structure. These results were compared with the effects induced by d-amphetamine. Plasma concentrations of phenylalanine and tyrosine were determined from blood samples taken immediately after behavioral examination. Data analysis revealed that these doses of aspartame, phenylalanine, and tyrosine did not induce any significant changes in spontaneous behavior. Unlike low doses of amphetamine and despite high plasma concentrations of phenylalanine and tyrosine, no behavioral alteration was detected by the computer pattern recognition system. Absence of behavioral changes in this study using an objective analysis of behavior raises questions concerning the relationship between amino acid precursor loading and purported anecdotal changes in behavior following aspartame administration.

Animals↗

PubMed1990

An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: effects on behavior.

Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

Animals↗

PubMed1989

Time structure analysis of behavioral acts using a computer pattern recognition system.

The spontaneous behavior of rats was monitored, classified and analyzed using a recently developed computer pattern recognition system. The K-function, a parameter developed for statistical research on spatial point processes and patterns, is used to analyze the temporal structure of behavioral acts or the joint relationship of separate acts. Forty male rats were observed in two experiments. In Experiment 1 untreated rats were observed and the temporal structure of their behavior was analyzed to establish an estimate of the false-positive error rate appropriate for use in such analyses. In Experiment 2, 20 control rats and 20 rats exposed to 2.0 mg/kg d-amphetamine were monitored using the computer pattern recognition system. The data from Experiment 1 showed that the false-positive rate was approximately ten percent or less. Experiment 2 demonstrated that the temporal structure of spontaneous motor behavior of amphetamine-treated rats was significantly disrupted.

Animals↗

PubMed1989

Extension of the analysis of the time structure of behavioral acts.

A parameter known as the K-function has previously been used to analyze the temporal structure of behavioral acts. In earlier work the study of these acts or of the joint relationship of separate acts has used a restricted list of activities whose definitions are difficult to explicate. In the present study this technique has been extended to a more extensive list of acts, each meaning of which is intuitively clear. As with the earlier work, the bootstrap method has been used to estimate the uncertainty in these measures, and the usefulness has been examined using data from studies of rats exposed to phenytoin or nitrous oxide.

Animals↗

PubMed1988

Analysis of the time distribution and time sequence of behavioral acts.

A technique for analyzing the temporal structure between various initiations of a particular behavioral act has been developed using a parameter known as the K-function, the cornerstone of recent statistical research on spatial point processes and patterns. The technique has been extended to the study of the joint relationship of separate acts. Bootstrap methods are used to estimate the uncertainty in these measures. The usefulness of these techniques is demonstrated using data from studies of rats exposed to phenytoin and nitrous oxide.

Animals↗

PubMed1987

Pattern recognition of rat behavior.

Analysis of animal behavior has been an arduous task requiring a human observer to record and classify individual motor acts. A computer pattern recognition system is introduced which simplifies this task by minimizing the need for human intervention. This system uses two video cameras with horizontal and vertical views of the behavior of a control and an experimental rat as they explore a simple environment for 15 minutes. Their behavior is sampled at a rate of one frame/second. Data from the video cameras are then converted into a form acceptable to Micro Vax I and VAX 11/750 computers. Each video picture is reduced to a 256 by 256 array, and ultimately each 15 minute observation session generates 28,800 blocks of information at 512 bytes each. Using a mathematically complete set of moments to the fourth order and the associated scalar invariants, the computer is programmed to identify the five major body positions of the rat including standing, sitting, rearing, walking and lying down. The computer also is programmed to identify the behaviors of grooming, head turning, whole body turning, looking, smelling, sniffing and washing face. This computer pattern recognition system not only speeds up behavioral classification, it alleviates the much criticized subjectivity introduced by human observers.

Animals↗

PubMed1986

The behavioral effects of prenatal and early postnatal lead exposure in the primate Macaca fascicularis.

Female Macaca fascicularis monkeys were given daily oral doses of 3.0 and 4.25 mg/kg lead, as lead nitrate, prior to breeding, and exposure was maintained throughout gestation and terminated at parturition. No overt signs of lead toxicity were observed in the maternal monkeys. The offspring were tested at 6 to 18 months of age on a three-choice non-spatial form discrimination paradigm, and at 19 to 26 months of age on a response inhibition task. When compared to controls, the lead-exposed infants showed a deficit in form discrimination performance which continued during the entire period of testing. A deficit in response inhibition performance was also observed in exposed infants when compared to controls. However, the deficit was temporary, as the performance of all groups was similar at the termination of testing. The observation of a persistent deficit in form discrimination up to 18 months following the termination of exposure suggests that lead-induced behavioral changes may be permanent. These findings are cause for concern since behavioral deficits in the offspring were observed at maternal gestational whole blood lead levels within a concentration range (30 to 70 micrograms/dl) associated with occupational exposure.

Animals↗

PubMedDate not supplied

Computer pattern recognition: an automated method for evaluating motor activity and testing for neurotoxicity.

An economical computer-based pattern recognition system, which has been designed to observe, classify, analyze, and record the spontaneous motor activity of the laboratory rat, is presented. The advantages and disadvantages of the system are assessed in terms of characteristics generally held to be desirable for a motor activity screen of potentially neurotoxic chemicals. Data from rats exposed to 1 mg/kg d-amphetamine are compared with similar data previously taken with an earlier version of the system at another laboratory.

Animals↗

PubMedDate not supplied

Neurotoxicity of sodium fluoride in rats.

Fluoride (F) is known to affect mineralizing tissues, but effects upon the developing brain have not been previously considered. This study in Sprague-Dawley rats compares behavior, body weight, plasma and brain F levels after sodium fluoride (NaF) exposures during late gestation, at weaning or in adults. For prenatal exposures, dams received injections (SC) of 0.13 mg/kg NaF or saline on gestational days 14-18 or 17-19. Weanlings received drinking water containing 0, 75, 100, or 125 ppm F for 6 or 20 weeks, and 3 month-old adults received water containing 100 ppm F for 6 weeks. Behavior was tested in a computer pattern recognition system that classified acts in a novel environment and quantified act initiations, total times and time structures. Fluoride exposures caused sex- and dose-specific behavioral deficits with a common pattern. Males were most sensitive to prenatal day 17-19 exposure, whereas females were more sensitive to weanling and adult exposures. After fluoride ingestion, the severity of the effect on behavior increased directly with plasma F levels and F concentrations in specific brain regions. Such association is important considering that plasma levels in this rat model (0.059 to 0.640 ppm F) are similar to those reported in humans exposed to high levels of fluoride.

Animals↗