Biomedical subjects

V C Moser

Publications and source records attributed to V C Moser.

At least 55 records · Page 3Linked to original sources

PubMed1992

Paraoxon toxicity is not potentiated by prior reduction in blood acetylcholinesterase.

The role of blood acetylcholinesterase in moderating the effects of organophosphate challenge in rats was tested. Adult male rats (n = 42) were injected (iv) either with monoclonal antibodies (MAb) to rat acetylcholinesterase (EC 3.1.1.7; AChE) or normal mouse IgG (controls). Two days later, the rats were injected (sc) with either a mild (0.17 mg/kg) or moderate dosage (0.34 mg/kg) of paraoxon or with vehicle. Neurological integrity was assessed by a functional observational battery followed by motor activity, 3 to 4 hr after dosing. Blood, brain, and diaphragm tissues were then collected for determination of AChE activity. MAb treatment reduced whole blood and plasma AChE activity by 32 and 90%, respectively, but did not affect neurobehavioral parameters or the AChE activity of brain or diaphragm. The paraoxon challenge produced dose-related neurobehavioral changes and inhibition of brain and diaphragm AChE activity to the same extent in IgG- and MAb-treated rats. Thus, significant loss in blood AChE alone produced no detectable neurobehavioral deficits and did not alter the subsequent responses to paraoxon challenge.

Acetylcholinesterase↗

PubMed1992

Comparison of subchronic neurotoxicity of 2-hydroxyethyl acrylate and acrylamide in rats.

The comparative neurotoxicity of subchronic exposure to 2-hydroxyethyl acrylate (HEA) and acrylamide (ACR) was evaluated using a functional observational battery (FOB) and neuropathology. Three dose levels of each compound (HEA: 3, 20, 60 mg/kg; ACR: 1, 4, 12 mg/kg) were administered intraperitoneally to male and female Long-Evans rats (n = 10/sex/dose level), 5 days/week for 13 weeks. Two vehicle control groups were also included. The FOB, which includes home-cage and open-field observations and interactive tests of sensory, neuromuscular, and autonomic function, was administered before dosing, at monthly intervals, and on the day after the last dose. Subsets of rats (n = 6/sex/dose level) were then perfused and tissues from the brain, spinal cord, and peripheral nerve were prepared for light microscopic evaluation. There were clear differences between the effects of HEA and ACR. ACR produced time- and dose-related changes in FOB measures of muscle tone and equilibrium, and produced axonal degeneration in peripheral nerves and within long tracts of the spinal cord. HEA exposure was also associated with changes in muscular function on FOB testing, but the magnitude of the effects was not as great as with ACR and not dose related. In addition, no neuropathological changes were detected after HEA exposure. Thus, the effects of HEA did not resemble those of ACR. The FOB data were summarized in domains of neurobehavioral functions. Using a composite score analysis, ACR was shown to produce prominent effects in the neuromuscular domain whereas HEA was largely without effect. When the data are analyzed in this manner, the neurotoxic potential of HEA appears to be minimal.

Acrylamide↗

PubMed1992

International validation of a neurobehavioral screening battery: the IPCS/WHO collaborative study.

A neurobehavioral screening battery consisting of a functional observational battery (FOB) and an automated measure of motor activity is the subject of an international collaborative study. Eight laboratories (four in Europe, four in the U.S.) are participating in this study, which is sponsored by the International Programme on Chemical Safety within the World Health Organization. Representatives from each laboratory received training on testing procedures and the study protocol during a 2-day workshop. Each laboratory then conducted studies using positive control chemicals to demonstrate their proficiency with the techniques. For motor activity studies, each laboratory had to show acute increases and decreases in activity produced by triadimefon and chlorpromazine, respectively. Using the FOB, each laboratory had to detect certain neurological syndromes: tremorigenic activity of a single dose of p,p'-DDT, cholinergic signs with parathion, and neuromuscular deficits with short-term (1-2 weeks) repeated administration of acrylamide. In the formal studies, the effects of seven chemicals are currently being determined following both acute and 4-week exposures. The chemicals include triethyl tin, acrylamide, parathion, p,p'-DDT, toluene, lead acetate, and N,N'-methylene bisacrylamide. All chemicals were provided to the laboratories from a single supplier. Each laboratory is conducting the studies under their standard conditions, using their own strain of rat and testing equipment. Each laboratory also determines a maximum-tolerated dose for each compound as well as the time of peak effect following acute exposure. A simple algorithm is then used to select doses for the formal acute and repeated-exposure experiments. These studies will provide information regarding the reliability and robustness of neurobehavioral screening methods over a wide range of laboratory conditions.

Animals↗

PubMed1992

Comparison of screening approaches.

Neurobehavioral techniques have been used extensively in animal toxicology studies because, in many cases, such procedures are designed to evaluate neurobiological functions thought to be affected in chemical-exposed humans, e.g., changes in sensorimotor function. Procedures used to identify or screen for the presence of neurotoxicity are usually designed to test large numbers of animals and are not considered to be as sensitive to subtle effects as more specialized tests for neurobiological dysfunction. For purposes of screening, the use of a functional observational battery (FOB) is now generally accepted. In general, FOB evaluations in animals are similar to clinical neurological examinations in humans in that they rate the presence and, in some cases, the severity of behavioral and neurological signs. A number of batteries containing different observations and measurements have been developed in several laboratories for rodents, dogs, and non-human primates. Frequently, the FOB is used in conjunction with other measures of neurotoxicity, i.e., neuropathology or sensory evoked potentials. FOB used in screening typically assess several neurobiological domains including neuromuscular (i.e., weakness, incoordination, abnormal movements, gait, motor seizures, myoclonia, rigidity and tremor), sensory (i.e., auditory, visual and somatosensory) and autonomic (i.e., pupil response, salivation) functions. Most FOB used for screening do not assess cognitive function (i.e., learning and memory). FOB evaluations can yield important information concerning dose-response characteristics and data on the onset, duration and persistence of an effect. FOB should be able to differentiate neurotoxicants from non-neurotoxicants and neurotoxicants having different mechanism(s) or site(s) of action.

Animals↗

PubMed1991

Rat strain and stock comparisons using a functional observational battery: baseline values and effects of amitraz.

A functional observational battery (FOB) was utilized to assess the effects of 3-day exposure to the formamidine pesticide amitraz in outbred Sprague-Dawley-derived and inbred Fischer-344-derived (F344) rats (both from Charles River Laboratories) and in outbred Long-Evans rats obtained from two commercial suppliers (Charles River Breeding Laboratories and Blue Spruce Farms). Significant strain and stock differences were obtained in baseline values for one-third of the FOB measures. In most cases, F344 rats were different from the others. Characteristic signs of amitraz exposure consisting of increased excitability, hyper-reactivity, and physiological and autonomic changes were evident in all treated rats. These effects increased with repeated dosing, and many were still present 6 days after dosing. On individual measures, there were differences between the strains and stocks in terms of sensitivity and time course of amitraz effects. In general, Blue Spruce Long-Evans rats displayed more effects of amitraz and F344 rats recovered more quickly than others. Although Sprague-Dawley rats showed the least effect overall, they displayed the largest increases in the sensorimotor responses to stimuli. These data indicate that although some behavioral and physiological parameters showed strain and supplier differences, in both baseline values and the effects of amitraz, conclusions concerning its neurotoxic potential in a screening context would be similar.

Animals↗

PubMed1991

Investigations of amitraz neurotoxicity in rats. IV. Assessment of toxicity syndrome using a functional observational battery.

A Functional observational battery (FOB) was utilized to provide a semiquantitative description of the hyperreactivity, excitability, and debilitation produced by amitraz. Adult male Long-Evans rats were administered either vehicle or 10, 25, 50, 100, or 200 mg/kg amitraz ip. They were tested with the FOB immediately before dosing, at 1 and 4 hr, and at 1, 2, 4, and 8 days after dosing. Higher doses (100-200 mg/kg) produced increased reactivity to manipulation, tenseness, and aggression. Most or all doses produced depressed arousal and rearing activity, hypothermia, body weight loss, and autonomic changes including ptosis, chromodacryorrhea resulting in facial crustiness, loss of the pupil reflex, and decreased defecation. Altered gait and decreased landing foot splay were also produced by amitraz. For the most part, effects of lower doses (10-50 mg/kg) were reversible by 2 to 4 days after treatment. In the higher dose groups, however, signs of toxicity were evident, and in some cases even more prominent (e.g., handling hyperreactivity), 8 days after a single dose of amitraz. The FOB thus provided a semiquantitative description of the magnitude and time course of many features of the amitraz toxicity syndrome.

Animals↗

PubMed1990

Comparative sensitivity of neurobehavioral tests for chemical screening.

Guidelines for conducting neurobehavioral tests of motor activity, schedule-controlled operant performance, and a functional observational battery (FOB) were published by the U.S. EPA Office of Toxic Substances (1985). We have utilized a specific FOB protocol in conjunction with motor activity measured in a figure-eight maze and performance maintained under a fixed-interval schedule of reinforcement to determine the acute effects of chemicals which produce different syndromes of intoxication in rats (chlordimeform, carbaryl, pentobarbital, triadimefon, nicotine, and 3-acetyl pyridine). The results showed that for each compound there was a substantial degree of overlap in the dose range of effectiveness across the different tests. In all cases, however, the lowest effective dose identified using the FOB was equal to or less than that provided by motor activity and operant tests. For most compounds, motor activity and operant performance were equally sensitive. Nicotine and triadimefon, however, increased the rate of operant responding at lower doses than those that affected motor activity. The time course of each chemical appeared similar across tests with one exception. 3-Acetyl pyridine produced clear effects in the FOB throughout testing (up to three weeks) whereas recovery was evident within one week using motor activity and operant performance. FOB and motor activity testing can be easily integrated into ongoing toxicity studies. On the other hand, the traditional approach to testing the effects of chemicals on operant performance requires prior food or water deprivation, and time for training the animals and establishing a stable level of performance. In the context of hazard identification (i.e., testing for the effects of unknown chemicals) the FOB and motor activity may be expected to adequately detect neurotoxicity. Operant performance may be more valuable in characterizing the actions of identified neurotoxicants.

Animals↗

PubMed1989

Investigations of amitraz neurotoxicity in rats. III. Effects on motor activity and inhibition of monoamine oxidase.

The formamidine pesticide amitraz (AMZ) produces many behavioral and physiological changes in rats. We examined the dose effect and time course of AMZ on motor activity, monoamine oxidase (MAO) activity, and acetylcholinesterase (AChE) activity to evaluate possible neurochemical mechanisms for the behavioral effects of AMZ. For motor activity studies, male Long-Evans hooded rats were tested in photocell activity measurement devices. AMZ produced dose-related decreases in motor activity of rats allowed free access to food and rats maintained at a stable body weight through food restriction. Lowest effective doses of AMZ tested were 1-3 mg/kg, administered 20 min before testing. AMZ appeared to be about three times more potent in food-restricted rats, indicating that amount of body fat may play a significant role in the pharmacokinetics of AMZ. Motor activity returned to control levels over 4-5 days after dosing with 100-200 mg/kg AMZ, whereas recovery was evident the day after administration of low doses (1-30 mg/kg). Inhibition of MAO was measured in whole brain of rats sacrificed at various times after dosing with AMZ. Only greater than or equal to 100 mg/kg AMZ inhibited MAO, which was measurable within 2 hr of dosing and lasted up to 7 days. AMZ appeared to be more selective for type B MAO when given in vivo, although MAO-A was also inhibited at doses greater than or equal to 300 mg/kg. However, no selectivity was indicated by the IC50 values determined in vitro (IC50 = 31 and 28 microM for MAO-A and MAO-B, respectively). AMZ produced only negligible inhibition of AChE at the highest doses administered in vivo or at 10 mM in vitro. These data indicate that while AMZ does inhibit MAO, the dose range over which it produces this action is much higher than that which suppressed motor activity. Thus MAO inhibition is probably not responsible for AMZ-induced alterations in motor activity.

Animals↗

PubMed1988

An alpha 2-adrenergic mode of action of chlordimeform on rat visual function.

The hypothesis that chlordimeform increased the amplitude of components N1P1 and P1N3 in rat pattern-reversal visual evoked potentials through actions on alpha 2-adrenergic receptors was tested with two sets of experiments. First, rats received single injections of either vehicle, an alpha 2-adrenergic antagonist yohimbine (0.1, 0.5, or 2.0 mg/kg), or an alpha 2-adrenergic agonist clonidine (0.05, 0.1, or 0.5 mg/kg). Yohimbine alone had no effect on pattern-reversal evoked potential amplitude. Clonidine treatment produced a dosage related increase in amplitude of both components similar to that produced by chlordimeform (W.K. Boyes and R.S. Dyer, 1984, Brain Res. Bull., 10, 817-823). Second, rats were given double injections of either vehicle or yohimbine (0.05, 0.5, 2.0, or 5.0 mg/kg) followed by either vehicle, clonidine (0.1 or 0.2 mg/kg) or chlordimeform (10, 20, or 40 mg/kg). Yohimbine pretreatment attenuated the effects of subsequent treatment with either clonidine or chlordimeform. These results support the hypothesis that chlordimeform alters rat pattern-reversal evoked potentials through actions as a central nervous system alpha 2-adrenergic agonist.

Amidines↗

PubMed1988

Comparison of chlordimeform and carbaryl using a functional observational battery.

The effects of the formamidine pesticide chlordimeform (CDM), and the carbamate carbaryl (CAR) were compared using a functional observational battery (FOB). The FOB, a series of observations and measurements that can be rapidly administered to toxicant-treated rats, includes home-cage and open-field observations, neuromuscular and sensorimotor tests, and physiological measures. Evaluations were made according to U.S. Environmental Protection Agency testing guidelines so as to determine dose-, time-, and sex-related toxicant effects. Long-Evans hooded rats of both sexes were tested initially and then dosed ip with either vehicle, CDM (1, 25, 56 mg/kg) or CAR (3, 10, 30 mg/kg), and tested at various times after dosing (for CDM 1, 5, 24 hr; for CAR 0.5, 3, 24, 48 hr). Both compounds affected general activity (home-cage and open-field), equilibrium, CNS excitability, and sensory responsiveness. Whereas similar decreases were obtained on rearing, gait, and arousal, there were important qualitative differences in the effects of CAR and CDM on reactions to handling and the reflex tests in that CDM increased excitability and enhanced responses to several stimuli but CAR either had no effect or decreased these measures. Only CDM produced an increase in muscle tone as measured by grip strength, and only CAR produced cholinergic autonomic signs of intoxication. Body weight and temperature were decreased by both compounds. Thus, the profiles of effect produced by these two pesticides could be clearly differentiated using the FOB.

Amidines↗

PubMed1987

Cholinergic involvement in the action of formetanate on operant behavior in rats.

Formetanate (FMT) is a formamidine acaricide/insecticide with a carbamate moiety in its molecular structure. FMT-induced lethality is reportedly due to inhibition of acetylcholinesterase. Here we report evidence of the neurochemical basis for the sublethal, behavioral effects of FMT in rats. In this experiment, 0.5 mg/kg of FMT (5 min before the 55-min test session) produced a pronounced suppression of response rates in rats trained to lever-press under a multiple fixed-interval 1-min fixed-interval 5-min schedule of milk reinforcement. Injections of scopolamine (0.1 mg/kg) and methylscopolamine (0.1 mg/kg) 15 min before FMT blocked the response rate suppression, whereas pretreatment with either mecamylamine (2 mg/kg) or hexamethonium (2 mg/kg) did not. These data suggest that FMT acts as an indirect agonist on central and peripheral muscarinic receptors, by inhibiting acetylcholinesterase, to produce changes in schedule-controlled responding.

Animals↗

PubMed1987

Investigations of amitraz neurotoxicity in rats. I. Effects on operant performance.

Amitraz (AMZ) is a formamidine pesticide which is often compared to chlordimeform (CDM). The effects of AMZ (6.25-75 mg/kg) and CDM (5-20 mg/kg) on the schedule-controlled performance of rats were examined using a multiple fixed-ratio (FR) 10 fixed-interval (FI) 300-sec schedule of milk reinforcement. Following dose-effect determinations, rats received three daily doses of AMZ (50 mg/kg). Low to intermediate doses of AMZ (6.25-25 mg/kg), administered 20 min presession, significantly decreased FI responding but not FR responding. In contrast, CDM appeared to decrease responding similarly under both components. Both compounds disrupted the temporal pattern of responding within the interval; AMZ had only a moderate influence at all effective doses but CDM produced a marked dose-dependent disruption of temporal response patterning. The effects of the high doses of AMZ (50-75 mg/kg) were more pronounced 24 hr after dosing, whereas the rats had recovered from lower doses at this time. Performance was progressively disrupted and the rats' health rapidly deteriorated during the course of three daily injections of AMZ (50 mg/kg). Operant performance recovered more quickly than did the general health of the rats. Thus AMZ produced effects of multiple-schedule performance that were distinct from the effects of CDM. Moreover, the signs of intoxication and the effects on schedule-controlled behavior following a high dose (50 mg/kg) were augmented and persistent with short-term repeated administration.

Animals↗

PubMed1987

Investigations of amitraz neurotoxicity in rats. II. Effects on visual evoked potentials.

As a part of a series of studies investigating the possible neurotoxicity of amitraz (AMZ), a formamidine pesticide, visual evoked potentials were recorded from Long-Evans rats following acute and short-term repeated exposures to AMZ. The first of three experiments examined the relationship between a single ip injection of AMZ (0, 50, and 100 mg/kg) and the latency and peak-to-peak amplitude of pattern-reversal (PREP) and flash-evoked potentials (FEP). The effects of another formamidine, chlordimeform (CDM; 40 mg/kg), were also studied for comparison purposes. Two hours after treatment, AMZ exposure produced large, dose-related increases in PREP amplitudes. Exposure to CDM produced similar changes. Neither compound changed FEP amplitudes. Body temperatures were reduced and evoked potential peak latencies were increased by both compounds. The latency increases were probably a secondary consequence of hypothermia. In the second experiment, PREPs were recorded before and 2, 24, 48, and 72 hr after treatment with AMZ (100 mg/kg). The time course of changes was biphasic in nature, with increases in amplitudes (N1P1, P1N2, and N2P3) 2 hr after treatment followed by subsequent depression in amplitude (P2N3) at 48 hr. Recovery occurred by 72 hr after treatment. The third experiment examined the effects of three daily treatments with either vehicle or 50 or 100 mg/kg AMZ. Body weights and body temperatures showed dose-related reductions which progressed with each additional treatment and recovered partially by 6 days after cessation of treatment. The PREPs of AMZ-treated rats agains showed biphasic changes, with N1P1 and P1N2 amplitudes significantly increased on each day of treatment and 1-2 days following the third treatment. Amplitude P2N3 showed an initial increase on the first 2 days of treatment, followed by subsequent, progressive amplitude reductions. In summary, AMZ produced two phases of change in visual evoked potentials. The first phase was characterized by large increases in PREP amplitudes without increasing FEP amplitudes in the same rats. The second phase was characterized by suppression of PREP P2N3 amplitude. Short-term repeated exposure produced signs of accumulating intoxication including progressive loss of body weight, lowered body temperature, and prolonged duration of evoked potential changes.

Animals↗

PubMed1987

Pentobarbital discrimination in the mouse.

Mice have rarely been used for drug discrimination research. A procedure is described for training mice to discriminate sodium pentobarbital (PB) from vehicle and the pharmacological specificity of the PB stimulus was assessed by generalization testing with methohexital, ethanol, chlorpromazine and morphine. Mice were trained to discriminate PB from vehicle using a two-lever procedure with responding maintained under a fixed-ratio 20 schedule of milk presentation. Training was initiated with 10 mg/kg PB or saline given i.p. 20 min prior to the sessions, and stimulus control was assessed every third session during 2-min periods when responding on either lever was reinforced. After 48 training sessions, good stimulus control had not been achieved. The PB dose was increased to 15 mg/kg, and after 12 additional training sessions, a mean accuracy of 93.5% and 88.1% was obtained on PB and saline tests, respectively. Generalization tests for the time course of the PB stimulus indicated that over 90% PB-lever responding occurred with pretreatment times of 5, 10 and 20 min, falling to 25.6% by 40 min and 15.4% by 60 min. Dose-dependent generalization was also obtained with doses of 15, 20 and 30 mg/kg occasioning over 75% and doses of 5 and 10 mg/kg occasioning less than 25% PB-lever responding. The mice also generalized from PB to methohexital and ethanol, although with the latter greater than 90% PB-lever responding was only produced by a dose that substantially decreased overall rates of responding. Generalization was not obtained with morphine nor chlorpromazine. Typical drug discrimination procedures utilized for pigeons, rats and monkeys can also be used with mice.

Animals↗

PubMed1986

Differential effects of formamidine pesticides on fixed-interval behavior in rats.

Chlordimeform (CDM), amitraz (AMZ), and formetanate (FMT) are members of the formamidine class of pesticides. To date, effects on operant behavior have been determined only for CDM. This experiment compared the effects of CDM, AMZ, and FMT on schedule-controlled responding. Nine male Long-Evans rats were trained during 1-hr sessions to lever-press under a multiple fixed-interval (FI)-1-min FI-5-min schedule of milk reinforcement. Dose-effect determinations for each compound administered ip, 20 min presession, were carried out in each subject. The dose ranges were: CDM HCl, 0.3-20 mg/kg; FMT HCl, 0.03-0.75 mg/kg; and AMZ, 5-75 mg/kg. Under baseline conditions response rates were higher under the FI-1-min than under FI-5-min, and index of curvature (IOC) values (a measure of within-interval response patterning) were generally higher under FI-5-min. All compounds produced dose-dependent decreases in response rate. CDM significantly decreased only FI-1-min response rates; a similar effect of AMZ was seen only at an intermediate dose. FMT decreased responding to the same extent in both components. CDM produced pronounced changes in the pattern of responding in both components, with IOC decreased more under FI-5-min than under FI-1-min. AMZ produced significant decreases in IOC only under FI-5-min. FMT did not appreciably decrease IOC in either component. High doses of AMZ produced general signs of poor health that persisted for several days. In addition, a greater effect on response rates and IOC in both components was obtained when AMZ (75 mg/kg) was given more than 10 days following another dose compared to when it was given 7 days or less after another dose. Formamidine pesticides produce differential effects on FI schedule-controlled behavior that are in turn modulated by the parameter value of the FI schedule.

Amidines↗

PubMed1985

Effects of xylene isomers on operant responding and motor performance in mice.

Xylene, a widely used industrial solvent, is a mixture of the ortho-, meta-, and paraisomers. In this study we examined the effects of each individual isomer, as well as a commercial-grade mixture of xylenes, on two behavioral measures: (1) operant performance of 15 mice trained to lever-press under a DRL (differential reinforcement of low rates) 10-sec schedule, and (2) motor performance of mice on an inverted screen test. The 15-min operant sessions immediately followed 30-min exposures to solvent vapors (500 to 7000 ppm), or air, in static inhalation chambers. All mice were exposed to each isomer in a counterbalanced order, and the mixture was given last in all cases. Ortho-, meta-, para-, and mixed xylenes produced similar biphasic effects on response rates, and concentration-dependent decreases in reinforcement rates. The lowest significantly effective concentration for each isomer on any variable was 1400 ppm, where increases in response rates occurred. Half-maximal response rate decreases were produced by 5179 ppm (ortho-xylene) to 6176 ppm (meta-xylene). The temporal distribution of responses was only moderately disrupted, even at high concentrations. In other groups of mice, motor coordination was also disrupted by the xylenes in a concentration-dependent manner. Half-maximal effective concentrations were 2676 ppm (para-xylene) to 3790 ppm (meta-xylene). Minimally effective concentrations were 2000 to 3000 ppm, higher than those seen in the operant studies. Xylene produced pronounced behavioral actions following acute exposure and no substantial differences in overall effects, and only slight potency differences, were obtained between the individual isomers or the commercial mixture.

Animals↗

PubMed1985

Monoamine oxidase inhibition cannot account for changes in visual evoked potentials produced by chlordimeform.

Chlordimeform (CDM), a formamidine insecticide and monoamine oxidase (MAO) inhibitor, has recently been shown to produce large changes in visual evoked potentials of hooded rats (Boyes and Dyer, 1984a). Two experiments were performed to determine if the changes in evoked potentials were a result of the inhibition of MAO. In the first, the degree of inhibition of MAO in the brains of rats treated with chlordimeform (1.0-100 mg/kg, i.p.) was compared with that produced by pargyline (0.3-30 mg/kg, i.p.). Both compounds preferentially inhibited MAO-B, although MAO-A was substantially inhibited at larger doses. Pargyline was a relatively more potent inhibitor of MAO than chlordimeform, but not more efficacious. In the second experiment, pattern reversal evoked potentials (PREPs) and flash-evoked potentials (FEPs) were recorded from groups of rats after treatment with either saline, 0.4 mg/kg pargyline, 20 mg/kg pargyline or 40 mg/kg chlordimeform. The latter two groups were selected so as to have similar levels of inhibition of MAO, about 90% inhibition of MAO-B and 60% inhibition of MAO-A. The results showed a doubling of the amplitude of pattern reversal evoked potentials and increased latencies of the pattern reversal evoked potential and the flash-evoked-potentials in the chlordimeform-treated group, but no significant changes from saline control values in the pargyline-treated groups. These results confirm that chlordimeform is a MAO inhibitor at doses which produce behavioral and electrophysiological changes, but demonstrate further that the changes in visual evoked potentials produced by chlordimeform are not a direct result of the inhibition of MAO.

Amidines↗

PubMed1985

Acute motor and lethal effects of inhaled toluene, 1,1,1-trichloroethane, halothane, and ethanol in mice: effects of exposure duration.

Some acute effects of inhalation exposure to toluene, 1,1,1-trichloroethane (1,1,1-TCE), halothane, and ethanol were examined in mice. Lethality and performance on an inverted screen test of motor performance were measured following 10-, 30-, and 60-min exposures. Concentration-dependent effects were obtained on both measures for all solvents except that lethal concentrations of ethanol could not be produced under these exposure conditions. Lethality increased with longer exposures for toluene, 1,1,1-TCE, and halothane. Sensitivity to the motor effects of 1,1,1-TCE, halothane, and ethanol increased when exposure duration was increased from 10 to 30 min, with no further change with 60-min exposures. In contrast, behavioral sensitivity to toluene increased over the entire range of exposure durations. The relative lipid solubilities of the solvents correlate with potency for behavioral activity but not as well with potency for lethality. The ratio of potency for motor and lethal effects depended on the chemical studied and in some cases exposure duration. These results demonstrate that both concentration and exposure duration determine the effects of inhaled compounds, but a simple linear relationship does not exist and it depends upon the effect measured.

Animals↗