Two experiments were conducted to determine the effects of hypothermia and pentobarbital anesthesia, alone and in combination, on the brain-stem auditory evoked responses (BAERs) of rats. In experiment I, unanesthetized rats were cooled to colonic temperatures 0.5 and 1.0 degrees C below normal. In experiment II, 2 groups of rats were cooled and tested at 37.5, 36.0, 34.5 and 31.5 degrees C. One group was anesthetized during testing and the other group was awake. The rat BAER was sensitive to cooling of 1 degree C or less. Peak latencies were prolonged and peak-to-peak amplitudes were increased by hypothermia alone. The effect on amplitude may be related to the time course of temperature change or to stimulus level. Pentobarbital significantly affected both latencies and amplitudes over and above the effects of cooling. The specific effects of pentobarbital differed by BAER peak and by temperature. The findings point up the importance of the potential confound of anesthetic drugs in most of the evoked potential literature on hypothermia and, for the first time, quantify the complex interactions between pentobarbital and temperature which affect the BAER wave form.

Anesthesia↗

PubMedDate not supplied

Depressed excitability and integrated EEGs following hippocampal afterdischarges.

Rats with chronic hippocampal electrode implants had afterdischarges induced with electrical stimulus intensities of 115, 200, and 800% of a previously determined threshold. Afterdischarge duration, postictal EEG depression duration, and the duration of postictal electrical hypoexcitability were assessed. After discharge duration varied inversely with stimulus intensity as did the duration of postictal hypoexcitability. However, the duration of postictal EEG depression increased with stimulus intensity. This dissociation between postictal neuroexcitability and EEG depression is discussed in terms of possible underlying cholinergic mechanisms.

Animals↗

PubMedDate not supplied

Increased hippocampal excitability produced by amitraz.

The present study characterized the effect of the formamidine pesticide, amitraz, upon hippocampal function in male Long-Evans rats. Animals were chronically prepared with a stimulating electrode in the perforant path and field potentials were recorded from a bipolar electrode situated across the granule cell layer of the dentate gyrus. Input/output functions and paired pulse inhibition were monitored in unrestrained, unanesthetized animals over a number of days following acute administration of 100 mg/kg of amitraz. Input/output functions revealed a decrease in excitatory postsynaptic potential (ESP) slope and an increase in population spike height 4 and 24 hr after treatment, with return to baseline by 48 hr. Tests of inhibition using pairs of stimulus pulses delivered at intervals ranging between 20 and 100 msec revealed a decrease in inhibition following amitraz. Both of these effects could be mimicked by administration of 0.1 mg/kg of the alpha-2 agonist clonidine, supporting this mode of action of amitraz on CNS function. These results indicate that systemic amitraz treatment produced a transient enhancement of excitatory and reduction of inhibitory processes in a CNS pathway.

Animals↗

PubMedDate not supplied

Acute exposures to p-xylene and toluene alter visual information processing.

Long-Evans hooded rats were exposed to single doses of toluene (PO) at 0, 250, 500 and 1000 mg/kg, to p-xylene (PO) at 0, 125, 250, 500, 1000 and 2000 mg/kg, and to inhalation of p-xylene for 4 hr at 0, 800 or 1600 ppm. The functional integrity of the visual system was evaluated using flash-evoked potentials (FEPs). The data indicated a significant depression in amplitude of FEP peak N3 at 250 mg/kg and higher dosages of toluene and p-xylene. A similar depression in peak N3 amplitude was observed following inhalation exposure to 1600 ppm p-xylene. The effects produced by oral administration of 500 mg/kg p-xylene or toluene lasted at least 8 hr, while the effect of inhaled p-xylene dissipated within 75 min of removal from the exposure. FEP peak N3 is presumed to be related to arousal, such that increases in arousal from a relaxed state should decrease amplitude. Rats administered amphetamine in dosages of 0.6, 1.2 and 2.5 mg/kg (known to increase arousal) also had reduced N3 amplitude. The effects of p-xylene and toluene on FEPs, while indicative of altered processing of visual information, may be secondary to changes in arousal or excitability.

Amphetamine↗

PubMedDate not supplied

Effect of perinatal monosodium glutamate administration on visual evoked potentials of juvenile and adult rats.

Administration of high doses of monosodium glutamate (MSG) to rats during the first postnatal week results in severe losses of retinal ganglion cells and interneurons in the retina. This study was conducted to determine what effect severe retinal damage would have upon the ontogeny of rat flash evoked potentials (FEPs) and the adult pattern reversal evoked potential (PREP). MSG (4 mg/g) or isotonic saline was administered to rat pups daily from postnatal day (PND) 2 until PND 9. FEPs were recorded following 2 stimulation frequencies from unanesthetized, unrestrained MSG treated and control rats on PND 15, PND 22, and PND 60 or older. PREPs were recorded from unanesthetized, restrained rats older than PND 60 from each treatment group. On PND 15, 9 of 12 control animals exhibited responses to light flashes, while only 4 of 13 MSG treated animals did so. All animals from both treatment groups exhibited FEPs on PND 22 and beyond. All FEP peak latencies were significantly increased in MSG treated animals with the magnitude of the effect being greater during development. Peak N1 amplitude was reduced in MSG treated animals by 50% or more at each age. Frequency x treatment interactions were observed on peak P2 and peak N3 latency, and a frequency x age x treatment interaction was observed on peak N3 amplitude. MSG treatment severely impaired the ability to generate PREPS. Only small responses to the pattern reversal stimulus could be detected and the normal PREP peaks could not be identified with confidence. Perinatal MSG treatment results in profound alterations in FEP ontogeny and the generation of PREPs.

Aging↗

PubMedDate not supplied

Sulfolane effects on audiogenic, pentylenetetrazol and afterdischarge seizure activity.

Sulfolane dosages that alter seizure susceptibility were determined using audiogenic (AG), pentylenetetrazol (PTZ) and hippocampal afterdischarge (AD) seizure models. The presence of AG seizures and potentiation of PTZ seizures were investigated in rats injected IP with 0, 200, 400 or 800 mg/kg; AD activity was assessed only at the highest and lowest dosages. The dose-dependent hypothermia associated with sulfolane treatment was controlled in Experiment I and a replication study (Experiment II) by testing under isothermic conditions. The effect of body temperature was measured directly in Experiment III by comparing AG seizure incidence and characteristics exhibited by hypothermic and normothermic animals. Audiogenic seizures were elicited in nearly half of the 800 mg/kg animals in both Experiments I and II. Sulfolane-induced hypothermia, maximal at 3 hours, partially protected against AG seizure characteristics. Potentiation of PTZ seizure severity (800 mg/kg) and duration (800 and 400 mg/kg) also were observed. None of the hippocampal AD parameters was affected significantly by sulfolane treatment. The similarity of the convulsants sulfolane and PTZ is discussed.

Acoustic Stimulation↗

PubMedDate not supplied

Acute sulfolane exposure produces temperature-independent and dependent changes in visual evoked potentials.

Sulfolane (tetrahydrothiophene-1, 1-dioxide) is a commercially important solvent. This report describes the consequences of acute exposure to sulfolane upon the visual system, as measured using flash evoked potentials (FEPs) and pattern reversal evoked potentials (PREPs). A single injection of either 1/2 or 1/4, but not 1/8 the IP LD50 (1600 mg/kg) produced significant changes in both FEPs and PREPs which were apparent within 1 hour and lasted longer than 6 hours. Amplitudes of FEP peaks to the first of a pair of stimuli were generally increased compared to control, an effect which was not temperature-dependent. In addition, sulfolane produced an ambient temperature- and dose-dependent hypothermia. Sulfolane increased latencies of FEP and PREP peaks, but attenuating hypothermia eliminated the effect of sulfolane on latencies.

Animals↗

PubMedDate not supplied

Septotemporal gradients of trimethyltin-induced hippocampal lesions.

Rats were administered 6 mg/kg trimethyltin (TMT) PO, and sacrificed at various time points (up to 60 days) for pathological evaluation. Studies along the full extent of the septotemporal axis revealed region-specific and cell field-specific damage. Dentate granule cells were most affected at the temporal pole and were only minimally affected at the septal pole. CA3c pyramidal neurons were affected along the full extent of the septotemporal axis. CA3a and CA3b pyramidal cells were most affected in the septal pole, and virtually unaffected in the temporal pole. It is suggested that CA3a and CA3b pyramidal cell damage may be dependent upon functionally intact granule cells.

Animals↗

PubMedDate not supplied

Neurophysiological effects of 30 day chronic exposure to toluene in rats.

Long-Evans hooded rats were exposed to 1000 ppm toluene or 0 ppm toluene 6 hr/day, 5 days/week for 30 days. Following removal from the exposure conditions (18-26 hr) flash-evoked potentials were recorded to paired light flashes and pentylenetetrazol (PTZ) seizure properties were examined. No alterations were found in the response to the first flash, but alterations in the recoverability of the nervous system were demonstrated by significant latency shifts in the response to the second of the paired flashes, using first flash latencies as covariates. No significant alterations were found in PTZ seizures. The data indicated that at these exposure levels toluene produced a small but significant alteration in brain function, even after toluene had been completely metabolized.

Animals↗

PubMedDate not supplied

Trimethyltin reduces recurrent inhibition in rats.

Rats with electrodes chronically implanted in the perforant path for electrical stimulation, and dentate gyrus for recording were treated with a single oral administration of either saline, 5 mg/kg trimethyltin (TMT) or 6 mg/kg TMT. Recurrent inhibition was assessed by paired pulse activation of the perforant path input to the dentate gyrus. The measure of recurrent inhibition employed was the ratio of the population spike amplitudes of the responses to the first and second of the paired stimuli. Inhibition was assessed immediately before, and at 2, 24 and 120 hr following TMT. The results indicated a reduction in inhibition as early as 2 hr following treatment, suggesting that TMT-induced destruction of hippocampal pyramidal cells may be secondary to their over-activation from an uninhibited mossy fiber system.

Analysis of Variance↗

PubMedDate not supplied

Cross species extrapolation and hazard identification in neurotoxicology.

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Animals↗