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Biomedical subjects

B M Kulig

Publications and source records attributed to B M Kulig.

34 records · Page 2Linked to original sources

Attenuation of phenobarbital-induced deficits in coordinated locomotion during subacute exposure.

The effects of phenobarbital on coordinated locomotion were measured in rats trained to criterion to avoid electric shock by running treadmill fashion along a motor driven belt. Two phenobarbital groups (35 and 50 mg/kg) and saline controls were injected for 29 consecutive days. Testing was carried out on Drug Days 1, 15, and 29. On Drug Day 1, disturbances in gait and balance were reflected by an increased time off belt for the phenobarbital groups. In addition, both groups demonstrated a significant improvement in performance over the three 2-min trial test sessions. Deficits were further reduced on Drug Day 15, and by Drug Day 29, the performance of rats treated with 35 mg/kg was equivalent to control values while that of the 50 mg/kg group had improved by more than 90%. There was no corresponding change in plasma levels of phenobarbital during subacute dosing. After a one month drug withdrawal period, treatment with phenobarbital again produced coordination deficits which were equivalent to those seen on Drug Day 1. These data demonstrate that an attenuation of the effects of phenobarbital on coordination can begin within minutes of the initial test session and is most likely due to behavioral processes (i.e., acute functional tolerance). In addition, results suggest that further drug exposure may play a role in the carry-over of functional tolerance from one drug test session to the next.

Analysis of Variance↗

The automated analysis of coordinated hindlimb movement in rats during acute and prolonged exposure to toxic agents.

The effects of CNS-active drugs and neurotoxic agents on motor coordination in the rat were studied using a newly developed, automated technique. In this test, a tv/microprocessor-based system was utilized to detect and describe the movement and placement characteristics of one of the rat's hindpaws as the rat placed its paw from one rung to another while walking in a rotating wheel. In studies employing a wheel speed of 8.2 cm/sec and a single 90-sec trial, significant deficits in coordinated hindlimb movement could be detected following the acute ip administration of a variety of compounds, including acrylamide (0, 50, and 100 mg/kg), diazepam (0, 0.5, 1.0, and 2.0 mg/kg), ethyl alcohol (0, 600, 900, and 1200 mg/kg), and tremorine (0, 2.5, 5.0, and 10.0 mg/kg). Further, results from a subacute study involving the oral administration of 2,5-hexanedione (2,5-HD; 0, 250, and 600 mg/kg) indicated that rats treated with 600 mg/kg, 2,5-HD were significantly impaired after 1 week of treatment and those treated with 250 mg/kg 2,5-HD, after 2 weeks of treatment. Although both groups improved during the recovery period, the performance of the 600 mg/kg group 5 weeks post-treatment was still inferior to controls. Taken together, these studies indicate that the coordinated hindlimb placement test provides a reliable, sensitive, and rapid technique for quantifying deficits in motor coordination in the rat during acute and prolonged exposure to neurotoxic substances.

Acrylamide↗

Effect of di-n-propylacetate on the 'binding of GABA to synaptosome-enriched fraction of rat cerebral cortex.

The effect of di-n-propylacetate (DPA) on the 'binding' of gamma-aminobutyric acid (GABA) to a synaptosome-enriched fraction of rat cerebral cortex has been examined using differential centrifugation and double-isotope liquid scintillation spectrometry. DPA at 10(-4) M caused a slight decrease in GABA binding. This effect could explain in part the in vivo anticonvulsant and behavioral effects of this drug when administered to animals in high systemic doses.

Aminobutyrates↗

Acute functional tolerance to the motor impairment effects of di-n-propylacetate.

Rats were trained to run treadmill fashion along a moving belt to avoid electric shock. After stabilization of performance, the effects of the anticonvulsant di-n-propylacetate (DPA; 100, 200 and 400 mg/kg) on treadmill locomotion were measured. Disturbances in gait and balance were reflected by an increased time off belt in a dose-related manner. In addition, animals showed a progressive improvement over the 3 two-min trials. A second experiment which measured the effects of 300 mg/kg DPA either 5 or 20 min postinjection revealed that the progressive improvement noted in the first experiment was not due to a diminished drug concentration or to an increased exposure to the drug. Thus, acute functional tolerance to the performance decrement produced by DPA appears to depend upon behavioural processes which enable an animal to overcome the drug-induced functional deficit by practicing the task while in the drug state.

Animals↗

The effects of chronic trichloroethylene exposure on neurobehavioral functioning in the rat.

Groups of rats were exposed by inhalation to either clean air (Controls) or trichloroethylene at 500, 1000 or 1500 ppm TCE for 16 hr/day, 5 days/week for 18 weeks. At preselected intervals, animals were evaluated for changes in: spontaneous activity, gripstrength, coordinated hindlimb movement, performance of a discrete-trial operant two-choice visual discrimination task, and peripheral nerve conduction velocity. Compared to Controls, TCE-treated rats showed no significant differences in open field behavior, fore- and hindlimb gripstrength or coordinated movement throughout the exposure period. Peripheral nerve conduction time was also unaffected. In contrast, TCE produced progressively marked changes in the speed and patterning of responding in the two-choice visual discrimination task. Two-choice response latency, for example, demonstrated an approximately four-fold increase (p less than 0.001) in the highest dose group. In addition, a recurrent within-week functional tolerance developed for all TCE-exposed groups. However, tolerance was lost in the TCE 1500 group as exposure became chronic. Finally, following the termination of exposure, there was no carry-over of TCE-related effects on any of the measures and performance quickly returned to baseline levels. This profile of effects argues for a primary involvement of the CNS with chronic TCE exposure and is quite unlike that seen with, e.g., n-hexane and carbon disulfide. Such findings underscore the differences in the effects which can be produced by long-term exposure to organic solvents and emphasize the need for a battery of tests in the evaluation of neurotoxicant-induced changes in nervous system functioning.

Action Potentials↗

The neurobehavioral effects of chronic styrene exposure in the rat.

Groups of rats were exposed by inhalation to either clear air (controls) or styrene monomer (STY) at 350, 700 or 1400 ppm for 16 hr/day, 5 days/week for 18 weeks. At preselected intervals, animals were evaluated for changes in: 1) spontaneous activity, 2) grip-strength, 3) coordinated hindlimb movement, 4) performance on a discrete-trial two-choice visual discrimination task, and 5) peripheral nerve conduction velocity. Compared to controls, STY-treated rats showed a mild but somewhat inconsistent reduction in activity and gripstrength during the course of exposure. Coordinated movement and peripheral nerve conduction time were unaffected. With respect to discrimination performance, exposure on Day 1 produced marked deficits in response speed and accuracy. By Day 2, deficits in discrimination performance were reduced by greater than 50% and the performance of STY-treated rats continued to improve as exposure continued. Finally, during the last weeks of exposure, the performance of STY-treated rats was equivalent to that of controls and no styrene-related deficits could be measured in the postexposure period.

Animals↗

Behavioral effects of exposure to organic solvents in Dutch painters.

The report describes the results of a cross-sectional study of solvent-exposed young and older Dutch painters and two age-matched control groups. Both traditional and computerized neurobehavioral tests were applied. The study did not detect any major differences between the two groups of painters and their two age-matched control groups. It is argued that this absence of differences is probably not due to a lack of sensitivity of the tests applied or the size of the groups studied. The level of exposure was estimated to be within a range at which previous authors have reported solvent-induced CNS effects.

Adult↗

Mid-frequency hearing loss and reduction of acoustic startle responding in rats following trichloroethylene exposure.

Modification of auditory evoked startle responding using prepulse inhibition was used to examine the effects of trichloroethylene (TCE) exposure on auditory thresholds. Rats were exposed by inhalation to 0, 1500, or 3000 ppm TCE for 18 hours per day, 5 days a week for 3 weeks. Auditory thresholds for 5 and 20 kHz tones were measured before exposure and at 1, 3, and 6 weeks postexposure. In addition, hearing thresholds for 5 and 35 kHz tones were examined at a 5-week postexposure time-point. Results indicated that hearing thresholds for 20 kHz but not for 5 or 35 kHz prepulses were significantly increased in rats exposed to 3000 ppm TCE. These findings demonstrate a selective hearing loss in the 20 kHz range by short-term, high-level TCE exposure. With respect to effects on startle responding per se, the present study also found that compared to controls, TCE-exposed rats failed to show an increase in baseline startle with repeated testing. This difference could not be attributed to differences in body weight and was persistent throughout the postexposure period.

Acoustic Stimulation↗

Symptoms indicative of the effects of organic solvent exposure in Dutch painters.

The report describes the results of a cross-sectional study among two groups of young and older painters and two age-matched control groups. The study was intended to gather information on the occurrence of solvent-exposure symptoms among Dutch workers using a mailed questionnaire. Results indicated that among young painters and to a lesser extent among older painters what is commonly accepted as specific symptoms and additional solvent-related symptoms showed a higher frequency than among the controls. The most interesting observation was a significant relationship between the frequency of periods of heavy exposure and the severity of most symptom categories, whereas there was a lack of consistent relationships with other exposure parameters.

Adult↗

Behavioral effects of exposure to organic solvents in carpet layers.

Carpet layers and age-matched controls were investigated both at the beginning of a working day and at the end with four subtests of a neuropsychological test battery (NES2). Exposure to toluene, cyclohexane, ethyl acetate, and heptane was measured with personal air sampling methods. One group of carpet layers used water-based adhesives (WBA) on the day the investigation took place and the other group used contact adhesives (CA) on that day. The WBA group was exposed primarily to toluene, and the CA group was exposed to other solvents as well. Initial (before work) differences in neuropsychological scores between all exposed workers and controls could be attributed to differences in education, the carpet layers being somewhat higher educated. No differences were found between the solvent-exposed and control groups that would suggest persistent effects of chronic solvent exposures. The improvement in test scores over the day was the same in both groups. However, evidence for exposure-related changes in test scores over the day were found within the exposed group.

Adhesives↗

Changes in regional brain GFAP levels and behavioral functioning following subchronic lead acetate exposure in adult rats.

Adult male WAG/Rij/MBL rats were dosed with lead acetate at 0, 4.0, 8.0 or 12.5 mg/kg, 5 days per week for 4 weeks. Animals were assessed prior to exposure, at the end of the 4-week exposure period and after a 2-week recovery period using a functional observational battery (FOB) and motor activity assessment. Rats were sacrificed two weeks after the last test session and glial fibrillary acidic protein (GFAP) concentrations were measured in eight selected brain regions. A dose-dependent decrease in motor activity was observed immediately following the end of the exposure period with no differences observed 2 weeks after cessation of exposure. Alterations in gait, decreased fore- and hindlimb grip strength, and decreased arousal were also found. Behavioral changes were accompanied by reduced weight gain and decreased body temperature during the course of exposure. GFAP concentrations were elevated in the frontal cortex, occipital cortex, striatum' and hippocampus but not in thalamus, cerebellum or brain stem. These results indicate that lead causes functional effects in the adult rat which can be detected by neurobehavioral methods. Furthermore, region-specific alterations in brain GFAP concentrations provided evidence of specificity of lead neurotoxicity in the adult brain.

Animals↗