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Biomedical subjects

D E Shearer

Publications and source records attributed to D E Shearer.

At least 37 records · Page 2Linked to original sources
PubMed1980

Naloxone-induced electrographic seizures in the primate.

Electrographic seizure activity was recorded shortly following naxolone injections in artificially ventilated, methadone-treated stump-tailed macaques. Plasma-methadone concentrations prior to seizure activity were many times higher than those that have produced respiratory depression and death in nonventilated monkeys. The duration of seizure activity was clearly related to the dose of naloxone. Naloxone was without epileptogenic properties in animals that had not been pretreated with methadone. The results suggest that methadone and naloxone have additive epileptogenic properties when high blood levels of methadone are achieved in the artificially ventilated primate. Naloxone was devoid of antagonistic properties with respect to opiate-induced electroencephalographic spiking activity.

Animals↗
PubMed1979

Methadone-induced changes in the visual evoked response recorded from multiple sites in the cat brain.

Visual evoked responses (VERs) and EEG were recorded following the i.p. administration of five doses of methadone (0.5--4 mg/kg) to 12 adult cats, which were implanted with cortical and subcortical electrodes. Additional cats, subjected to the same drug regimen, were used to evaluate plasma methadone concentrations. Doses of methadone that produced plasma concentrations between 80 and 190 ng/ml differentially affected VERs recorded from cortical and subcortical sites. Of the subcortical structures evaluated, the limbic system, specifically the hippocampus, was the most sensitive to the effects of the drug. These effects appeared to be primarily depressant. Responses recorded from the reticular formation and centromedian were affected only by the highest dose of methadone, while VERs recorded from cortical sites were reliably altered following the two highest doses and appeared to reflect both excitation and depression. Behavioral changes, however, were clearly evidenced in some cats at lower doses of methadone. Therefore, the data suggest (1) that those structures evaluated electrophysiologically did not reflect the full force of the drug's action as evidenced by its effect on behavior, (2) that cortical and subcortical recording sites have differential sensitivities, and (3) that one clearly defined, principal size of action of methadone is absent in the cat.

Animals↗
PubMed1978

Differential effects of convulsants on visually evoked responses in the albino rat.

Visually evoked responses (VERs) were recorded from primary visual cortex in unanesthetized albino rats during pharmacological modulation by one of the following convulsant agents: Physostigmine, picrotoxin, strychnine and Metrazol. The data were analyzed in terms of effects on VER components. The rat VER consists of six distinct waves constituted by three positive peaks (P1--P3) and three negative peaks (N1--N3). Results indicate a differential convulsant action on VER components. The administration of picrotoxin, resulted in a suppression of the peak amplitude of P1--N1 and delayed peak latencies of all components. Strychnine reliably shortened P1, N1 and P2 peak latencies, significantly increased N3 peak latency and only suppressed P3--N3 amplitude. Physostigmine essentially suppressed all component amplitudes but only increased peak latencies for P2 and P3 components. Metrazol, in general, was found to be relatively ineffective in the alteration of any VER component in a systematic manner. The data are discussed in terms of differential modes of convulsant action on the visual system. The results are likewise discussed with respect to their implications for convulsant modulation of photically evoked after-discharges.

Animals↗
PubMed1977

Visual evoked response and behavioral correlates of plasma methadone concentrations in cats.

Twelve cats were implanted with cortical and depth electrodes. After they recovered from the operation, visual evoked responses (VERs) were recorded at 20 min following saline and methadone (0.5, 1, 2, 3, 4 mg/kg) administered IP in a semi-random order to each cat. Four other cats were similarly drugged and plasma was obtained for radioimmunoassay of methadone content. At the three lowest dose levels behavioral excitation and salivation were evident in some cats, while their VER configuration remained essentially unaltered and plasma methadone was barely measurable. Following the 3 and 4 mg/kg doses plasma methadone concentration increased dramatically, behavioral excitation and salivation were evident in most cats and VERs were reliably altered. The VER alterations, consisting of amplitude attenuation and a decrease in some latencies, were restricted to secondary VER components occurring between 50 and 100 msec despite the animals' extreme behavioral excitation. These results suggest that the reticular formation is not a principal site of the drug's effect.

Animals↗
PubMed1976

Metrazol potentiated after-discharges: dose-response relationships and effects of selective lesions.

In Experiment 1 the dose-response effects of pentylentetrazol (Metrazol) on photically evoked after-discharge (PhAD) parameters were examined. Metrazol potentiated PhAD activity by affecting all measured parameters - PhAD frequency, amplitude, burst duration and spindle composition - in particular PhAD burt duration and spindle composition. A mimimum effective dose of 10 mg/Kg of Metrazol was required for some statistically reliable potentiation. Metrazol dosage levels of 20 and 25 mg/Kg induced lengthy bouts of EEG spindling and spiking as well as near maximized PhAD component augmentation. In Experiment 2 stereotaxically oriented knife-cuts isolated the thalamus from cortical and/or midbrain and brainstem input. Such lesions did not block the capacity of Metrazol to potentiate PhADs, although the lesions altered evoked activity. These findings are discussed in terms of the current thought of Metrazol action and thalamic mechanisms in the control of after-discharge activity.

Animals↗
PubMed1976

Differences in cytochrome P-450 of various strains of rats following chronic administration of pentobarbital.

Cytochrome P-450 levels were analyzed in rats of two pigmented (black Long-Evans and ACI) and two albino strains (Fischer 344 and Sprague-Dawley) following the administration of pentobarbital sodium and physiological saline. Differences between the albino vs pigmented strains were observed following injections of saline. The Fischer 344 albino strains responded similarly to the pigmented strains following a progressively increasing dose schedule of pentobarbital sodium.

Animals↗
PubMed1976

The photically evoked afterdischarge: a model for the study of drugs useful in the treatment of petit mal epilepsy.

Lightly restrained albino rats were administered dipropylacetic acid, trimethadione, diphenylhydantoin, saline, and a pentylenetetrazol challenge. The results were attributed to the locus of action of the anticonvulsants and strongly support the usefulness of the photically evoked after discharge as a model for the evaluation of thalamically active drugs, with particular reference to those useful in the control of petit mal epilepsy.

Animals↗
PubMed1976

A miniature, readily available electrode pedestal for recording cerebral and other electrophysiological activity from several species.

A miniature, commercially available electrode pedestal with prewired and prenumbered leads was designed. It possesses long-term electrical reliability and can be applied to a wide range of animal species. It can be easily modified to record electroencephalograms, evoked responses, and related physiological measurements. The device is relatively small, with keyed and lock-down parts, and is resistant to damage.

Animals↗