Biomedical subjects

R S Dyer

Publications and source records attributed to R S Dyer.

At least 37 records · Page 2Linked to original sources

PubMed1986

Amygdaloid kindling increases enkephalin-like immunoreactivity but decreases dynorphin-A-like immunoreactivity in rat hippocampus.

The effects of amygdaloid kindling on the regional levels and distribution of enkephalin-like and dynorphin-A (DN)-like immunoreactivity (LI) were examined. One day after completion of kindling, radioimmunoassay revealed a 71% decrease in DN1-8-LI and a 43% increase in [Met5]-enkephalin-LI in the hippocampus. Immunostaining revealed a depletion of DN1-17-LI in the hippocampal mossy fiber pathway and an increase in [Leu5]-enkephalin-LI in the temporoammonic pathway. Four weeks after completion of kindling, the levels and immunostaining intensity of dynorphin and enkephalin in the hippocampus had returned to control values.

Amygdala↗

PubMed1986

Unrecognized errors due to analog filtering of the brain-stem auditory evoked response.

Analog filtering of the brain-stem auditory evoked response (BAER) and synthetic wave forms using steeply sloped filters are shown to produce significant distortion even when filter cut-off frequencies are well removed from the wave form spectrum. The degree of distortion is such that it may result in erroneous identification of peaks in the BAER. Reversal of the order of peaks may occur with high pass settings at only 1/4 the lowest constituent frequency. Filter effects were identified as a major source of cross-laboratory differences in BAERs recorded from laboratory rats. Filter transfer functions of a typical analog filter set were derived for both gain and phase as a function of frequency. Filtering of synthetic wave forms was used to elucidate and highlight distortion effects. A typical Long-Evans rat BAER wave form was spectrum analyzed and conclusions were drawn with respect to appropriate bandpass frequencies.

Analog-Digital Conversion↗

PubMed1986

Superior colliculus lesions and flash evoked potentials from rat cortex.

It is generally assumed that the primary response of the rat flash evoked potential (FEP) is activated by a retino-geniculate path, and that the secondary response reflects input to the cortex by way of the superior colliculus (SC) or other brainstem structures. In the present study, male Long-Evans rats were implanted with monopolar screw electrodes placed over the left visual cortex, and a pair of twisted monopolar depth electrodes, which were used to produce electrolytic lesions, were placed in each SC. One half of the animals did not receive the electrolytic treatment (controls). FEP waveforms were obtained from all animals prior to treatment, and 2 and 5 days after treatment. Histological analysis was performed to verify electrode placement and determine lesion size. Electrolytic lesions resulting in massive destruction of the SC produced no decrement in any portion of the rat FEP but did produce an increase in amplitude of the N2P3 component. The data show that the secondary response is not generated by SC in rats, but that SC may modulate amplitude of the response.

Animals↗

PubMed1986

Sulfolane-induced hypothermia enhances survivability in mice.

Mice injected intraperitoneally with sulfolane (tetrahydrothiophene-1,1-dioxide) underwent a significant decrease in metabolic rate and body temperature at ambient temperatures of 20 and 30 degrees C but not 35 degrees C. If given the opportunity, mice treated with sulfolane preferentially sought a cool ambient temperature. When given an LD50 dose of sulfolane (1270 mg/kg), the percentage mortality varied directly with ambient temperature. For example, at 35 degrees C mortality was 75% whereas at 25 degrees C mortality was only 8%. By undergoing an autonomically and behaviorally mediated decrease in body temperature (i.e., regulated hypothermia), sulfolane-treated mice appear to enhance their chance of survival.

Animals↗

PubMed1985

Chlordimeform produces contrast-dependent changes in visual evoked potentials of hooded rats.

Previous experiments found that acute exposure to the insecticide/acaricide, chlordimeform (CDM), produced large increases in the amplitude of pattern reversal evoked potentials (PREPs) without changing the amplitude of flash evoked potentials (FEPs) in the same rats (W. K. Boyes and R. S. Dyer, Exp. Neurol. 86: 434-447, 1984). Current work investigated the influence of physical characteristics of the evoking stimuli on the action of CDM. Adult male Long-Evans rats with epidural visual cortex electrodes were used. In experiment 1, PREPs were elicited with alternating gratings having equal contrast (99%) and a square wave spatial luminance profile at several spatial frequencies. Rats treated 1 h previously with 40 mg/kg CDM had increased PREP amplitudes at 0.1, 0.2, and 0.4 cycles per degree (cpd), but not at 0.8 cpd. No changes were found after 5 mg/kg CDM. In experiment 2, PREPs were elicited with gratings oriented at 0 degrees (horizontal), 45 degrees, 90 degrees, or 135 degrees. Treatment with 40 mg/kg CDM increased PREP amplitudes and latencies regardless of orientation. In experiment 3, FEPs elicited with strobe flashes spanning four log units of intensity showed a small but significant CDM dose X intensity interaction on P2N2 peak-to-peak amplitude. In experiment 4, PREPs were elicited with alternating gratings having a sinusoidal spatial luminance profile, spatial frequency of 0.2 or 0.8 cpd, and contrast ranging from noise levels to 65%. Rats treated with 40 mg/kg CDM showed increased peak-to-peak amplitudes only at 0.2 cpd and only at contrast values above 10%. The failure of CDM to alter PREPs at 0.8 cpd was attributed to low contrast sensitivity at that spatial frequency. The results demonstrated that the action of CDM on visual evoked potentials was dependent on the amount of contrast in the stimulus pattern, and suggested that CDM alters the encoding of visual contrast.

Amidines↗

PubMed1985

Body temperature-dependent and independent actions of chlordimeform on visual evoked potentials and axonal transport in optic system of rat.

Pattern-reversal-evoked potentials (PREPs), flash-evoked potentials (FEPs), rapid axonal transport in the optic system and body temperature were measured in hooded rats, treated with either saline or the formamidine insecticide/acaricide, chlordimeform (CDM). Rats receiving chlordimeform had low body temperatures when housed at standard laboratory room temperature, 22 degrees C, but not at 30 degrees C. Peak latencies of flash-evoked potentials were prolonged by chlordimeform at 22 degrees C, but not at 30 degrees C. The rate of axonal transport was slowed in chlordimeform-treated hypothermic rats, but not in chlordimeform-treated warmed rats. These findings suggest that the flash-evoked potential and axonal transport changes produced by chlordimeform were an indirect consequence of hypothermia. In contrast, chlordimeform increased pattern-reversal evoked potential peak latencies and peak-to-peak amplitudes independent of body temperature. These findings confirm and extend previous reports of chlordimeform-induced hypothermia, emphasize the importance of changes in body temperature as a possible confounding factor in studies of neuroactive agents and demonstrate that chlordimeform has both body-temperature-dependent and independent actions in the visual system in the rat.

Amidines↗

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

Neurophysiological consequences of acute exposure to methylpyridines.

A series of neurophysiological tests was performed on Long-Evans hooded rats treated with either 2-, 3-, or 4-methylpyridine at dosages of 100 mg/kg, approximately one-half the ip LD50. The tests contained measures of sensory function (paired pulse flash evoked potentials, pattern reversal evoked potentials, and brainstem auditory evoked responses) and cerebral excitability (pentylenetetrazol seizures and hippocampal afterdischarges). In general, rats treated with 2- and 3-methylpyridine were more affected than those treated with 4-methylpyridine. The changes observed were in many ways similar to those seen following administration of depressant compounds: increased latency of evoked potentials and increased latency to PTZ seizures. Not all findings, however, were consistent with previously observed patterns of central nervous system depression.

Animals↗

PubMed1985

Acute behavioral toxicity of sulfolane: influence of hypothermia.

Sulfolane is a solvent which produces hypothermia and decreased oxygen consumption following acute exposure. In the present experiment, we investigated effects of sulfolane on a behavioral measure of toxicity at ambient temperatures which would either prevent or facilitate the development of hypothermia. Adult male Long-Evans rats (N = 10/dose) received a single i.p. injection of saline, 200, 400 or 800 mg/kg sulfolane. Motor activity in figure-of-eight mazes was assessed 1 h after dosing in testing rooms maintained at either 20.8 degrees C or at 32.3 degrees C. At the warm ambient temperature, sulfolane produced hypoactivity but not hypothermia. At the cooler temperature, sulfolane-induced hypoactivity was more pronounced, and rats were hypothermic. Therefore, a behavioral change could be detected at sublethal dosages of sulfolane in the absence of hypothermia.

Animals↗

PubMed1985

Effect of sulfolane on behavioral and autonomic thermoregulation in the rat.

Sulfolane (tetrahydrothiophene 1,1-dioxide), a commonly used extraction solvent, promotes rapid changes in the thermoregulatory system. Colonic temperature, skin temperature, metabolic rate, and preferred ambient temperature (Ta) were measured over an 8-h period in the Sprague-Dawley rat following an intraperitoneal injection of sulfolane at 800 mg/kg or of physiological saline. At Ta values of 15 and 25 degrees C, sulfolane caused a significant inhibition in metabolic rate and reduction in colonic temperature, which lasted over the 8-h measuring period. At both Ta values, metabolic rate tended to recover approximately 4 h after sulfolane injection. Colonic temperature recovered with time but was still significantly reduced at 8 h postinjection. Tail skin temperature was unaffected. Preferred Ta in the sulfolane-treated rat was not significantly different from the controls. In spite of their hypothermic condition, the sulfolane-treated animals did not select a warm Ta. Since sulfolane toxicity appears to be greater with increased tissue temperature, the sulfolane-induced hypothermia may enhance survival of the rat following exposure to toxic levels of sulfolane.

Animals↗

PubMed1985

Early effects of trimethyltin on the dentate gyrus basket cells: a morphological study.

Electrophysiological evidence for reduction of recurrent inhibition in the dentate gyrus in animals exposed to trimethyltin (TMT) suggested alterations in the inhibitory neurons (basket cells) by TMT. The present study was designed to investigate the morphology of basket cells after TMT exposure. Long-Evans hooded rats were injected with TMT chloride in a dose of 6.0 mg/kg body weight (b.w.). Tissue samples from the dentate gyri were examined by both light and electron microscopy at 24 and 72 h after TMT exposure. Except for isolated basket cell damage at 72 h, no remarkable pathological changes were observed with light microscopy. Consistent with previous data, electron microscopy revealed that the basket cells of the dentate gyrus are large neurons situated just below the granule cell layer with characteristic large, infolded nuclei and intranuclear filamentous rods. Increased cytoplasmic density and degenerative changes of the Golgi complex were evident in the basket cells as early as 24 h after TMT exposure. By 72 h, neuronal vacuolation, accumulation of lysosomes, and occasional neuronal necrosis were observed. No significant pathological changes were found among the granule cells at this time. This report provides the first morphological evidence for early damage to the basket cells by TMT, which may account for the reduction of recurrent inhibition and hyperexcitability among the granule cells reported previously.

Animals↗

PubMed1985

The use of sensory evoked potentials in toxicology.

The rationale for studying sensory systems as an integral part of neurotoxicological examinations is presented. The role of evoked potentials in assessing brain dysfunction in general and sensory systems in particular is also presented. Four types of sensory evoked potentials (brainstem auditory evoked response, somatosensory evoked potentials, flash evoked potentials, and pattern reversal evoked potentials) are discussed in terms of their demonstrated contributions to neurotoxicology and clinical neurology. Research needed to allow these methods to achieve their full value for neurotoxicology is identified and briefly discussed.

Acoustic Stimulation↗

PubMed1984

Effect of ambient temperature on the hypometabolic and hypothermic effects of sulfolane in rats.

Sulfolane toxicity may be partially due to its effects on body temperature. To examine the effects of sulfolane on thermoregulation, we measured metabolic rate (oxygen uptake) and body temperature in rats injected intraperitoneally with sulfolane at dosages of 0, 200, 400, and 800 mg/kg. At ambient temperatures (Ta) of 15 and 25 degrees C sulfolane caused a dose-related inhibition of metabolic rate accompanied by hypothermia 60 min post-injection. At a Ta of 35 degrees C, sulfolane had no effect on body temperature or metabolic rate. The hypometabolic and hypothermic effect of sulfolane at a Ta of 25 degrees C at least 2.5 h. Sulfolane had near identical effects on body temperature at TaS of 15 and 25 degrees C, hence, the sulfolane-treated rat had some control over body temperature at a relatively low Ta.

Animals↗

PubMed1984

Chlordimeform produces profound, selective, and transient changes in visual evoked potentials of hooded rats.

Rat visual function was tested after acute exposure to chlordimeform (CDM), a formamidine insecticide/acaricide. Adult male Long-Evans rats were surgically implanted with epidural recording electrodes overlying visual cortex and tested 1 week later. Pattern reversal-evoked potentials (PREPs), flash-evoked potentials (FEPs), and FEP recovery ratios were measured after acute CDM administration. Averaged recordings obtained during 200 reversals of a black-and-white square wave grating comprised the PREPs, and those obtained during 128 paired strobe lamp flashes comprised the FEPs. In the first study, which examined dose-response relationships, i.p. injections of 0 (saline), 5, 15, or 40 mg/kg CDM-HCl were administered 30 min prior to testing. The PREP amplitudes showed large dose-related changes in the CDM-treated rats. PREP N1P1 and P1N3 peak-to-peak amplitudes increased more than 200% in the 40 mg/kg group. In contrast, FEP amplitudes and FEP recovery ratios were unchanged by CDM. Both PREP and FEP peak latencies were increased by CDM in dose-related fashions. In the second study, which examined the time course of CDM action, PREPs and paired-pulse FEPs were recorded 3, 6, and 24 h after dosage with either 0 or 40 mg/kg CDM. All evoked potential changes were large at 3 and 6 h, but had returned to control values by 24 h. In summary, acute exposure to CDM temporarily increased both the amplitude and latency of PREPs, but only the latency of FEPs.

Amidines↗

PubMed1984

Effect of triethyltin on autonomic and behavioral thermoregulation of mice.

The organotin compound, triethyltin (TET), produces toxic effects in a variety of physiological systems. Thermoregulatory control appears to be especially susceptible to TET toxicity, since TET administration has been shown to cause a pronounced hypothermia in rats. To further elucidate effects of TET on thermoregulation, we measured metabolic rate, evaporative water loss (EWL), body temperature, and preferred ambient temperature (Ta) of mice treated intraperitoneally with TET (bromide salt). At a Ta of 23 to 24 degrees C, TET (6 and 8 mg/kg) inhibited metabolic rate by 23 and 66%, respectively. TET resulted in hypothermia at Ta's of 20 and 30 degrees C but not 35 degrees C. TET had little effect on EWL. Mice given TET at doses of 4, 6, and 8 mg/kg selected a cooler Ta (ca. 25 degrees C) compared to controls (ca. 29 degrees C). Thus, the mice selected a Ta associated with a hypothermic body temperature. At a relatively cool Ta, mice treated with TET had a reduced rate of heat production and, consequently, were hypothermic. At a relatively warm Ta, TET had no effect on heat production and did not increase active heat dissipation (i.e., EWL), thus the mice remained normothermic. The behavioral data indicate that TET evokes a type of regulated hypothermia in mice.

Animals↗

PubMed1984

Contribution of hypothermia to effects of chloral hydrate on flash evoked potentials of hooded rats.

This study examined the contribution of hypothermia to the effects of chloral hydrate on the flash evoked potential (FEP) of hooded rats. Three experiments were performed, all employing intraperitoneal injections of saline, and of 75, 150 and 300 mg chloral hydrate/kg body weight. In the first experiment, body temperature was measured in a standard (23 degrees C) environment for 6 hr following injection. Rats were hypothermic following administration of the 150 and 300 mg/kg dosages for up to 1 and 2 hr, respectively. In the second experiment, FEPs were recorded from the visual cortex of chronically implanted rats 30 min after injection (22 degrees C environment). P1N1, N1P2 and P2N2 amplitudes and P1, N1, P2, N2 and P3 peak latencies were significantly increased by the 300 mg/kg dosage. Increased latencies were also noted for the primary components with the 150 mg/kg dosage. The final experiment replicated the second experiment, but at an ambient temperature of 30 degrees C, which prevented hypothermia. Amplitudes were unaffected by chloral hydrate. Significantly increased peak latencies were observed, even with the 75 mg/kg dose for some components. However, the magnitude of the latency increases of the primary components was less than half of that found with a standard environment. These results indicate that depending upon ambient temperature, hypothermia may contribute to chloral hydrate-induced alterations in FEPs.

Animals↗

PubMed1983

Pattern reversal visual evoked potentials in awake rats.

A method for recording pattern reversal evoked potentials (PREPs) from awake restrained rats has been developed. The procedure of Onofrj et al. [26] was modified to eliminate the need for anesthetic, thereby avoiding possible interactions of the anesthetic with other manipulations of interest. Rats were restrained in a harness and placed in front of a pattern generating TV screen displaying a black and white alternating square wave grating. Using various stimulation and recording parameters, normative data are presented from 141 adult male Long-Evans hooded and 11 adult male Sprague-Dawley albino rats. Reliable waveforms were recorded with five identifiable peaks. The labels and mean latencies of these peaks in hooded rats were: N1, 47.3 msec; P1, 65.7 msec; N2, 83.3 msec; P2, 94.4 msec; and N3, 129.8 msec. Spatial acuity functions generated with PREPs gave acuity estimates which corresponded closely to values determined behaviorally for hooded and albino rats [4,11].

Animals↗

PubMed1983

Hypothermia and chloropent anesthesia differentially affect the flash evoked potentials of hooded rats.

Anesthetics and body temperature alterations are both known to alter parameters of sensory-evoked responses. However few studies have quantitatively assessed the contributions of hypothermia to anesthetic-induced changes. Two experiments were performed. In the first, chronically implanted rats were injected with either 0, 0.05, 0.10 or 0.20 ml Chloropent/100 g b.w., while body temperature was maintained. Flash evoked potentials recorded 30 min later showed increased latencies but only minor (not statistically significant) changes in amplitude. In the second experiment the same rats were anesthetized with 0.35 ml Chloropent/100 g b.w. and rectal temperature was systematically varied between 31 degrees C and 37 degrees C. Over the ranges of temperature and anesthetic employed, latencies increased more extensively with hypothermia than with anesthesia. P1N1 amplitude doubled when temperature was lowered to 31C, but P2N2 and N2P3 amplitudes declined over the same temperature range. Anesthetic-induced changes in peak-to-peak amplitude did not reach statistical significance when body temperature was constant. The findings suggest that previously reported alterations in evoked potentials following anesthesia may have been confounded with hypothermia.

Anesthetics↗