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Biomedical subjects

R M Joy

Publications and source records attributed to R M Joy.

At least 55 records · Page 3Linked to original sources
PubMed1983

Aminophylline and kindled seizures.

The effects of aminophylline on amygdaloid and cortically kindled rats was studied. Rats implanted with chronic amygdaloid electrodes received either saline or 150 mg/kg, i.p., aminophylline 20 min prior to their first stimulation. On the first stimulation, aminophylline-treated rats had dramatically longer afterdischarge durations and more severe seizure ranks. When fully kindled, the animals were retested with saline or aminophylline. Again, the aminophylline-treated animals had longer afterdischarge durations than the saline-treated rats. In a second experiment, fully amygdaloid kindled rats were pretreated with various doses of aminophylline and stimulated 20 min later. With suprathreshold stimulation, a dose-dependent increase was noted in the afterdischarge duration. During seizure threshold determinations, aminophylline pretreatment markedly prolonged afterdischarge durations without significantly changing seizure severity or threshold. When animals were treated with the adenosine agonist, 2-chloroadenosine, prior to kindled amygdaloid stimulation, the elicited afterdischarge was shortened. The effect was antagonized where treatment with both 2-chloroadenosine and aminophylline occurred prior to amygdaloid stimulation. Rats with neocortical electrodes were also exposed to various doses of aminophylline while in a stable, partially developed kindled stage and again when fully kindled. At both stages, afterdischarge duration was increased by aminophylline in a dose-dependent manner. The partially developed, cortically kindled animals were more responsive to aminophylline than were those fully kindled and they tended to have greater increases in afterdischarge duration and seizure rank. These data demonstrate that aminophylline acts to prolong afterdischarges elicited at various stages of kindling from both amygdaloid and cortical sites.

2-Chloroadenosine↗
PubMed1983

The effects of doxapram, diazepam, phenobarbital and pentylenetetrazol on suprathreshold and threshold stimulations in amygdaloid kindled rats.

Amygdaloid kindled rats were utilized to determine the effects of the respiratory stimulant, doxapram (7.5-60 mg/kg) on seizures elicited by suprathreshold or threshold electrical stimulation. For comparison, a single dose of pentylenetetrazol (30 mg/kg), phenobarbital (40 mg/kg) and diazepam (2 mg/kg) were also tested in the same paradigm. With suprathreshold stimulation, doxapram did not increase the intensity of seizures. Neither the afterdischarge duration (AD) nor the behavioral rank (BR) were increased with doses high enough to cause systemic signs of toxicity. Similarly, the convulsant pentylenetetrazol did not increase AD or BR after suprathreshold stimulation. The anticonvulsants phenobarbital and diazepam significantly reduced both AD and BR after suprathreshold stimulation. Seizure thresholds tended to be higher after the various doses of doxapram with no consistent effect on elicited AD or BR. Pentylenetetrazol did not change threshold values, but was found to increase AD and BR at threshold. Both phenobarbital and diazepam raised thresholds with a significant decrease in elicited AD and BR. It would appear that the respiratory stimulant doxapram has little proconvulsant activity in this model of epilepsy.

Amygdala↗
PubMed1983

Caffeine modification of kindled amygdaloid seizures.

Rats were kindled during exposure to caffeine (50 mg/kg) or saline given IP twenty minutes before daily electrical stimulation of the amygdala until 3 kindled amygdaloid seizures (KAS) occurred. They were then stimulated for 3 days without drug pretreatment followed by 5 additional days with drug pretreatment. There were no significant differences between the two groups in the number of daily stimulations or in the total seconds of cumulative afterdischarge (AD) needed to reach the first KAS. During kindling, the daily average AD tended to be longer in the caffeine treated group. This difference became significant (greater than 200% saline) when the KAS was reached. When KAS animals were stimulated without caffeine pretreatment, the average AD returned to control lengths. When put back on caffeine pretreatment, the average AD was again increased. Caffeine (6-50 mg/kg, IP) was also evaluated in previously kindled rats using suprathreshold (400 mu AMP) and threshold (20 microA increments) seizures. Caffeine had no consistent effect on threshold values. However, 12-50 mg/kg of caffeine increased seizure severity and AD durations after threshold stimulation. With suprathreshold stimulation, the length of the AD was significantly increased only after the highest dose of caffeine. It would appear that caffeine lengthens induced afterdischarges both during the acquisition phase of kindling and in the fully kindled subject. Caffeine does not appear to lower seizure thresholds or increase the rate of acquisition of the KAS in the doses tested in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1983

Dose-dependent proconvulsant and anticonvulsant actions of the alpha 2 adrenergic agonist, xylazine, on kindled seizures in the rat.

The effects of the alpha 2 adrenergic agonist, xylazine, was evaluated on kindling acquisition and on kindled seizure expression in rats. Dose-dependent proconvulsant and anticonvulsant properties were found. The proconvulsant effects were observed at low (0.3 mg/kg) doses. In previously kindled rats these consisted of a decrease in afterdischarge threshold and an increase in the length and severity of the accompanying seizure. This dose also facilitated the rate of kindling in naive subjects. The anticonvulsant effects were observed at higher dose levels (3-20 mg/kg) which also produced sedation and ataxia. If these effects upon kindling are related to the adrenergic actions of xylazine, then it is proposed that the proconvulsant effects are associated with alpha 2 receptor activation and the anticonvulsant effects with alpha 1 receptor activation.

Amygdala↗
PubMed1983

Proconvulsant actions of lindane: effects on afterdischarge thresholds and durations during amygdaloid kindling in rats.

Daily exposure to lindane, 5 mg/kg, produced a number of consistent changes in rats undergoing amygdaloid kindling. Lindane decreased the number of afterdischarge-evoking stimulations required to produce the fully kindled state, increased the length of each successive afterdischarge during kindling and increased the severity of each convulsive response during kindling. However, lindane exposure did not change the total seconds of afterdischarge activity required to create the fully kindled state. In this study the enhancement of kindling rates by lindane stemmed primarily from an increase in the duration of epileptiform activity following each amygdaloid stimulation. These proconvulsant effects cannot be attributed to a lowering of seizure thresholds by lindane. Thresholds evaluated at different times during and after completion of kindling were either unaffected or actually elevated by lindane exposure. The length and severity of seizures evoked in fully kindled subjects by amygdaloid stimulation were much less affected by lindane exposure. This indicates that the most useful period for demonstrating proconvulsant activity with the kindling seizure model is during the dynamic phase of seizure development. Once the process has reached completion, seizures are maximally expressed, and their duration is controlled by processes not as susceptible to lindane exposures.

Amygdala↗
PubMed1983

The persistence of kindled amygdaloid seizures in rats exposed to lindane.

The persistence of the kindled seizure state produced during exposure to 5 mg/kg/day lindane was compared to that produced in nonexposed subjects. Persistence was evaluated at intervals of 2 weeks and 2 months. Rats were kindled on corn oil alone or corn oil + lindane until each rat exhibited a fully kindled seizure. Two weeks later subjects were tested for persistence using a crossover design where half the lindane-kindled rats were retested under lindane and the other half under oil. Two months later, subjects were retested again, without further exposure. The results demonstrate that the kindled state during lindane exposure was equally as stable and persistent as that produced under control conditions. This was true even though kindling required about 40% fewer trials with lindane exposure than without. The equivalence of the control and lindane kindled state is an important finding. It suggests that the proconvulsant action of lindane on kindling is not simply an additive one. Rather, lindane appears to directly increase the rte at which the permanent alterations in neuronal connectivity occur which are responsible for kindling expression.

Amygdala↗
PubMed1980

The kindled seizure: production of and modification by dieldrin in rats.

In the rat dieldrin can evoke a progressive increase in the severity of convulsive responses (kindling) during repetitive exposures that cannot be attributed to simple accumulation of dieldrin in the brain. It can also replace pentylenetetrazol as a kindling stimulus in previously pentylenetetrazol-kindled rats (cross-kindling). Chronic exposure to dieldrin facilitates kindling produced by daily electrical stimulation of the amygdala. Even single, acute exposure, can facilitate kindling produced by electrical stimulation of the amygdala, 1 to 3 weeks later. We propose that the procedure of kindling is a useful one with which to assess neurotoxicity. Agents affecting kindling in laboratory animals are of particular concern to those individuals in a population with demonstrable seizure susceptibility, those predisposed to convulsive disorders and others vulnerable to increased levels of CNS excitability.

Amygdala↗
PubMed1978

Correlations between EEG and multiple unit activity of cortifugal axons at the onset of drug induced seizures in cats.

The onset of sustained multiple unit activity (MUA) in corticofugal axons was found to precede the onset of tonic EEG activity in 91 of 92 seizures produced by administering pentylenetetrazol, strychnine, or dieldrin to cats. Latency differences from 0-8 sec were observed with a mean of 3 sec. A trend was noted for shorter latencies with subsequent seizures in the same subject. No differences in latency were seen for spontaneous as compared to evoked seizures. Much variation was encountered in the pattern of MUA and EEG development at seizure onset. In general seizures with well-defined EEG components of desynchronization, tonic and clonic activity had the greatest latency differences and the least correspondence between MUA and EEG. Seizures with the abrupt emergence of tonic or clonic activity had the smallest latency differences and the best correspondence between MUA and EEG. Large changes in the activity along corticofugal axons were observed without EEG correlates. The evidence supports the concept that the degree of synchrony within the cortical (pyramidal) cell population is critical to the emergence and development of EEG during the tonic and clonic phases of a seizure. The data suggest that, in some cases, important changes in corticofugal output may contribute to and reinforce the activity in subcortical loci implicated in generalized seizure onset.

Action Potentials↗
PubMed1977

Magnesium modulation of glucose-induced insulin secretion by the perfused rat pancreas.

Increasing levels of magnesium were found to cause a marked depression of glucosestimulated insulin secretion at fixed calcium levels, particularly at levels which bracketed the concentration of ultrafiltrable magnesium found in normal rat plasma (1.3 meq/l), i.e., increasing magnesium from 0.6 to 1.2 meq/l depressed secretion, and increasing magnesium from 1.2 to 2.4 meq/l resulted in a further depression. Paradoxically, when magnesium was omitted from the perfusing medium, insulin secretion was also depressed. The data strongly suggest that the calcium/magnesium ratio is a primary regulator of the insulin secretory process, since a relatively slight alteration of the physiologic ratio of calcium to magnesium (approximately 2.5) results in a marked alteration of total insulin secretion. In addition, small amounts of magnesium are necessary for optimum secretion, possibly reflecting the requirement for magnesium in several enzymatic processes. Thus, magnesium may play an important role in the regulation of insulin secretion by altering the sensitivity of the beta cells of the Islets of Langerhans to glucose.

Animals↗