Search PubMed⌕ Search

Biomedical subjects

M E Corcoran

Publications and source records attributed to M E Corcoran.

At least 37 records · Page 2Linked to original sources
PubMed1995

Further characterization of kindling antagonism.

Alternating stimulation of two sites in the forebrain culminates in typical kindling of generalized seizures from one site (dominant), whereas the other site (suppressed) supports only nongeneralized seizures for as long as stimulation of the dominant site continues, a phenomenon referred to as kindling antagonism. With the termination of stimulation of the dominant site, however, seizures provoked from the suppressed site eventually generalize, a progression thought to reflect the resumption of kindling from a previous point of arrest. To further assess the nature of kindling antagonism, we established antagonism between the amygdala and the septal area and subsequently evaluated the development of seizures provoked by stimulation of sites distal to the dominant site (always the amygdala). In Experiment 1, a 30-d stimulation-free period imposed after the establishment of antagonism failed to result in immediate generalization of seizures provoked from the suppressed site (septal area) in seven of eight rats. Although these results suggest that antagonism reflects an actual arrest of kindling rather than a transient inhibition of seizures, they are not entirely unambiguous: Rats exposed to the prolonged stimulation-free period required only half the number of septal stimulations for the expression of a generalized seizure as compared to rats receiving septal stimulation immediately after the establishment of antagonism. The latter finding is suggestive of a transient component of antagonism. In Experiment 2, development of generalized seizures from the previously naive right amygdala was virtually identical in rats previously kindled from the left amygdala and in rats expressing antagonism between the septal area and left amygdala. Development of generalized seizures from the right amygdala was faster than from the left amygdala in both groups of rats, however, suggesting that the expression of seizures provoked from the suppressed site after the establishment of antagonism does not involve a general impairment or enhancement of transfer. Experiment 3 revealed that radio-frequency lesions of the dominant site (amygdala) after the establishment of antagonism did not alter the subsequent development of generalized seizures from the suppressed site (septal area). This suggests that the expression of generalized seizures from the suppressed site after the establishment of kindling antagonism is not dictated by the functional state of the dominant site.

Animals↗
PubMed1994

Pathway specificity of noradrenergic plasticity in the dentate gyrus.

Previous experiments have described highly specific effects of noradrenergic agonists on synaptic transmission in the dentate gyrus (DG). For example, perfusion of hippocampal slices with the beta-noradrenergic agonist isoproterenol induces a long-lasting potentiation (LLP) of extracellularly recorded responses following stimulation of the medial perforant path (PP), and long-lasting depression (LLD) of responses evoked by stimulation of the lateral PP (Dahl D, Sarvey JM, 1989, Proc Natl Acad Sci USA 86:4776-4780). To examine the possible interactions of LLP, LLD, and long-term potentiation induced by tetanic stimulation (LTP), the authors recorded extracellular field potentials evoked in the DG by stimulation of the lateral or medial perforant path following LTP and LLP or LLD, invoked in different orders. After establishment of LLP or LLD by bath application of isoproterenol, subsequent tetanization of the respective afferents resulted in additional potentiation of the medial PP-evoked response and return of the lateral PP-evoked response to baseline levels. In other slices, application of isoproterenol after establishment of LTP resulted in further potentiation of medial PP-evoked responses but no change in the potentiated response evoked by lateral PP stimulation. Thus the pathway specificity was maintained irrespective of the history of previous potentiation or depression. Experiments using the specific beta 1 antagonist metoprolol further confirmed pathway specificity. Perfusion with 20 microM of metoprolol appeared to reduce LTP evoked by stimulation of the medial but not lateral PP. In a subsequent experiment, metoprolol in the absence of tetanization produced LLD of the medial PP-evoked response and LLP of the lateral PP-evoked response, opposite to the effects of ISO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Infusions of alpha-2 noradrenergic agonists and antagonists into the amygdala: effects on kindling.

We reported previously that activation of alpha-2 adrenoceptors with infusions of clonidine into the amygdala/pyriform region is sufficient to retard kindling. To characterize further the involvement in kindling of alpha-2 receptors in the amygdala/pyriform, we exposed rats to unilateral intraamygdaloid infusions of a variety of noradrenergic drugs followed by either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Infusions and electrical stimulation were administered once every 48 h. The prophylactic effects of clonidine were blocked by simultaneous infusion of idazoxan, an alpha-2 adrenergic antagonist, which suggests strongly that these effects were produced at an alpha-2 receptor. Intraamygdaloid infusions of xylazine, another alpha-2 agonist, also significantly retarded low-frequency kindling. Unexpectedly, intraamygdaloid infusions of the alpha-2 antagonists idazoxan, yohimbine, and SK&F 104856 failed to accelerate kindling. Infusion of the alpha-1 antagonist corynanthine also failed to affect kindling. We propose that the alpha-2 adrenoceptors in the amygdala/pyriform region contribute to the prophylactic effects of systemically administered clonidine and that the facilitation of kindling observed after systemic administration of alpha-2 antagonists may be due to blockade of alpha-2 adrenoceptors outside of the amygdala/pyriform region.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1993

Kindling antagonism: mapping of susceptible sites.

Previous research has shown that concurrent alternating stimulation of paired limbic sites culminates in kindling of generalized seizures from 1 (dominant) site, whereas the other (suppressed) site supports only focal or partial seizures. This phenomenon has been referred to as kindling antagonism, and it has been proposed that antagonism reflects an arrest of kindling, which is therefore viewed as a non-continuous stepwise process. We have attempted to replicate these important observations in adult rats stimulated in various combinations of forebrain sites. Kindling antagonism was displayed by rats stimulated in the amygdala and the septal area, in the bilateral amygdala, the septal area and the splenium of the corpus callosum, and the amygdala and the cingulate cortex. We also found that antagonism between the amygdala and septal area as well as electrographic and behavioral correlates of alternating stimulation were sensitive to the hemispheric relation of the electrodes and to the order in which the sites received initial stimulations. That is, rats that carried ipsilateral amygdaloid and septal electrodes were less likely to display antagonism when the amygdala was the first site stimulated. On the other hand, we failed to obtain antagonism from rats stimulated in other limbic pairs (e.g. entorhinal cortex and septal areas.

Amygdala↗
PubMed1993

Differential effects of kindling and kindled seizures on place learning in the Morris water maze.

There is some controversy about the role of long-term potentiation (LTP) in spatial learning. The authors have found that triggering generalized kindled seizures with stimulation of the perforant path disrupts spatial learning in the Morris water maze but that kindling per se does not affect spatial learning. It is suggested that abnormal electrical activity induced by high-frequency stimulation of the perforant path may have been responsible for the disruption of spatial learning previously attributed to LTP saturation.

Animals↗
PubMed1993

CL 218,872 a triazolopyridazine with a selective affinity for the benzodiazepine BZ1 receptor subtype, retards the development and expression of amygdaloid-kindled seizures: effects of flumazenil.

To clarify the role of benzodiazepine receptors in kindling, the present experiment assessed the effects of CL 218,872 (1, 5, 10, and 20 mg/kg), a triazolopyridazine with a selective affinity for the putative benzodiazepine BZ1 receptor subtype, on the development and expression of amygdaloid-kindled seizures. Additionally, we assessed the effects of flumazenil (10 mg/kg), a non-specific benzodiazepine receptor antagonist, on kindling and the expression of kindled seizures alone or concomitantly with CL 218,872 (20 mg/kg). CL 218,872 retarded the development of kindled seizures in a linear dose-dependent manner; rats treated with 5, 10, and 20 mg/kg, but not 1 mg/kg, of CL 218,872 required a greater number of afterdischarges (ADs) to develop generalized seizures than controls. Flumazenil also retarded kindling and failed to attenuate the prophylactic effect of CL 218,872. In a cross-over procedure rats that did not develop generalized seizures after 30 ADs while under drug were rekindled under vehicle and rats kindled under vehicle were subsequently tested under drug. Rats crossed over to vehicle rekindled at a faster rate than did controls during initial kindling, suggesting that some kindling had occurred under the drug. CL 218,872 also dose-dependently depressed kindled seizures and this was attenuated by flumazenil, which had little effect on kindled seizures by itself. Together, these data suggest that CL 218,872 is a potent anticonvulsant, implicating the BZ1 receptor subtype in seizure development and in the expression of kindled seizures.

Amygdala↗
PubMed1992

Intra-amygdaloid infusions of clonidine retard kindling.

It has been reported previously that systemic administration of clonidine, an agonist of alpha-2 noradrenergic receptors, significantly retards amygdaloid kindling by delaying the emergence from partial seizure. We examined the effect of either systemic administration (i.p.) or intra-amygdaloid infusions of clonidine on the kindling of seizures with electrical stimulation of the amygdala. Rats received either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Clonidine and electrical stimulation were administered once every 48 h. We observed a significant retardation of kindling in rats receiving i.p. injections of clonidine (0.1 mg/kg) or infusions of clonidine in concentrations of 10(-7)-10(-4) M, regardless of the stimulation frequency. The prophylactic effect was due to a delay in the progression out of partial seizure. The effect was specific to the amygdala/pyriform region, because infusions of clonidine dorsal to the amygdala were without effect. Intra-amygdaloid clonidine had little effect on established generalized seizures, suggesting that it was producing a genuine prophylactic effect against kindling. We conclude that the subpopulation of alpha-2 adrenoceptors in the amygdala/pyriform region contributes to the antiepileptogenic effect observed after systemic administration of clonidine.

Amygdala↗
PubMed1992

Limbic seizures, but not kindling, reversibly impair place learning in the Morris water maze.

We investigated the effects of kindling and kindled seizures in different limbic structures on place and cue learning in the Morris water maze. The triggering of seizures by stimulation of the perforant path, septum, or amygdala prior to daily training impaired place learning, but had little effect on visible platform training or swim speed. Seizures triggered by stimulation of the medial perforant path after daily training also impaired place learning. Conversely, place learning proceeded normally in rats tested 24 h after kindling triggered by stimulation of the perforant path, septum, or amygdala, indicating that kindling per se does not affect place learning. Each group was able to learn the location of a reversed platform when pretraining seizures were discontinued; and perforant path and septal kindled rats, but not amygdaloid kindled rats, were impaired at learning the location of a reversed platform when seizures were triggered before training. The results confirm previous reports that limbic seizures produce amnesia, but they contradict the finding that hippocampal kindling impairs learning on tasks sensitive to hippocampal lesions.

Amygdala↗
PubMed1992

Characteristics of dorsal and ventral striatal kindling in rats.

We examined the characteristics of kindling of seizures with stimulation of the dorsal or ventral striatum in rats. Different groups of rats carried electrodes directed towards the nucleus accumbens or the head, middle, or tail of the caudate. Thresholds for afterdischarge (AD) were high at all sites, and stimulation often produced forced motor responses (motor responses that occurred during the stimulation and were not a consequence of kindling). Kindling at sites in the accumbens proceeded more slowly than at the sites in the caudate, which did not differ among themselves. The duration of accumbens seizures increased dramatically over the course of kindling, whereas the duration of caudate seizures remained relatively short and invariant. Although the kindled seizures resembled seizures kindled from limbic sites, they also contained aspects of seizures triggered from stimulation of the anterior neocortex. We conclude that striatal kindling comprises elements of both limbic and neocortical kindling.

Animals↗
PubMed1992

Reinforcing and punishing consequences of kindling.

The motivational consequences of kindling were examined in the conditioned place preference paradigm. In a distinctive environment, rats received stimulation of the amygdala that triggered afterdischarge (AD) alone or AD and generalized seizures. After 4 conditioning trials, preference for the conditioning environment or a control environment was measured. Amygdaloid ADs associated with nonconvulsive seizures (stage 0) produced a conditioned decrease in time spent in the initially preferred chamber by rats receiving stimulation there, and they produced a conditioned increase in time spent in the initially nonpreferred chamber by rats receiving stimulation there. These effects were not large, in that there was no overall mean shift from preference to avoidance, or vice versa; but they were reliable and significant. Similarly, stage 5 seizures produced a small and nonsignificant decrease in time spent in the conditioning chamber in which seizures were triggered. It appears that amygdaloid AD produces weak effects that are either reinforcing or punishing, depending on the behavioral baseline, and that generalized amygdaloid seizures are, at most, mildly punishing.

Amygdala↗
PubMed1990

Involvement of multiple opiate receptors in opioid kindling.

D-Tyr-Ser-Gly-Phe-Leu-Thr (DSLET), beta-endorphin, morphiceptin and morphine were microinjected at 48-h intervals into the amygdala or hippocampus of awake rats in an attempt to identify the opiate receptor types involved in opioid kindling. DSLET, beta-endorphin, morphiceptin and morphine were injected into the lateral ventricle to assess the possibility of kindling seizures by this route. The delta-receptor agonist DSLET effectively kindled convulsions when microinjected into amygdala or ventral hippocampus. The convulsions were suppressed or strongly attenuated by ICI 174,864, a specific antagonist of the delta-receptor, microinjected into the same brain site, but were not affected by ICI 174,864 administered peripherally. When microinjected into amygdala or hippocampus, beta-endorphin and morphiceptin also kindled convulsions, which were antagonized by naloxone but not by ICI 174,864. Morphine evoked EEG epileptiform activity but did not kindle convulsions from limbic brain sites. DSLET occasionally evoked epileptiform spiking and submaximal convulsions when injected into ventricle, and morphiceptin evoked epileptiform spiking only, but tolerance to these effects occurred after repetition of the injections. Thus, convulsions can be kindled by activation of either mu-, delta- or epsilon-receptors when opioids are injected directly into limbic tissue. However, the ability of these compounds to kindle seizures is markedly reduced when they are administered into ventricle. The striking differences between the present results and previous results obtained by peripheral or intraventricular administration of opioid peptides suggest that the route of administration, among other variables, is a crucial factor in assessing the epileptogenic properties of opioid peptides.

Animals↗
PubMed1990

Inhibition of phospholipase activity in human monocytes by IFN-gamma blocks endogenous prostaglandin E2-dependent collagenase production.

Previous studies from our laboratory have demonstrated that exposure of human monocytes to a stimulant, such as Con A, results in the production of the enzyme collagenase through PGE2-dependent pathway. Inasmuch as rIFN-gamma has been shown to modulate monocyte/macrophage PG synthesis, we examined the effect of rIFN-gamma on the activation sequence leading to collagenase production. The addition of rIFN-gamma (10 to 1000 U/ml) to Con A-stimulated monocytes resulted in a dose-dependent inhibition of PGE2 and collagenase synthesis. The suppression of collagenase production by rIFN-gamma was related to its ability to reduce PGE2 levels as demonstrated by the restoration of collagenase activity by the addition of PGE2. HPLC analysis of the arachidonic acid (AA) metabolites released by monocytes showed that rIFN-gamma caused a reduction in the release of AA and products of the cyclooxygenase and lipoxygenase pathways. These data indicated that rIFN-gamma decreased eicosanoid production by inhibiting the release of AA from phospholipids. This conclusion was supported by the reduction in membrane bound phospholipase activity in rIFN-gamma-treated monocytes. Moreover, the inhibition by rIFN-gamma of PGE2 and collagenase was reversed by the addition of phospholipase A2. Our findings demonstrate that rIFN-gamma inhibits phospholipase activity in activated monocytes and as a result blocks PGE2-dependent collagenase synthesis.

Cells, Cultured↗
PubMed1990

Kindling with stimulation of the dentate gyrus. I. Characterization of electrographic and behavioral events.

Once daily for 60 days, hooded rats received unilateral high-frequency stimulation in the hilus of the dentate gyrus (DG), at an intensity sufficient to evoke epileptiform afterdischarge (AD). Although most rats eventually developed generalized stage-5 seizures (Generalized group), some did not progress beyond partial stage-1 or stage-2 seizures (Partial group). Hilar kindling also displayed several other characteristics that distinguished it from typical limbic kindling, including low rate of development, marked instability of the seizures, and little or no growth in duration of AD.

Action Potentials↗
PubMed1990

Kindling with stimulation of the dentate gyrus. II. Effects on evoked field potentials.

Once daily for 60 days, male hooded rats received unilateral high-frequency stimulation in the hilus of the dentate gyrus (DG), at an intensity sufficient to evoke afterdischarge (AD). Every 2nd day, evoked potentials were recorded from the hilus following stimulation of the PP with single 0.1 ms pulses at 6 current intensities. Changes in synaptic excitability of the dentate granule cells were monitored by measuring the amplitudes of the population spikes; changes in the strength of excitatory synaptic transmission were monitored by measuring the slopes of the excitatory postsynaptic potentials (EPSPs). Control rats, which were not given kindling stimulation, were tested for changes in synaptic transmission and excitability in the same way, at comparable times. In general, hilar stimulation resulted in a large decrease in population spike amplitudes to below baseline and control levels, accompanied by a paradoxical potentiation of EPSPs. Population spike amplitudes decreased more in rats that developed generalized stage-5 seizures (Generalized group) than in rats that did not progress beyond partial seizures despite 60 days of stimulation (Partial group). Conversely, EPSP slopes increased more in the Partial group than in the Generalized group. These results suggest that kindling stimulation may potentiate responsiveness of the directly activated dentate granule cells to inputs from the PP, but at the same time suppress the output of the granule cells resulting from this input. Furthermore, the results indicate that kindling is more closely allied to the suppression of output than to the potentiation of responsiveness to input.

Action Potentials↗
PubMed1990

Antikindling effects of locus coeruleus stimulation: mediation by ascending noradrenergic projections.

Electrical stimulation of the noradrenergic locus coeruleus (LC) delays the generalization of partial seizures during amygdaloid kindling by increasing the time spent in the earliest stages of seizure development. To determine whether noradrenergic axons projecting to the midbrain and forebrain are involved in this antikindling effect, we examined the effects of lesions of the dorsal noradrenergic bundle, induced by intracerebral infusions of 6-hydroxydopamine (6-OHDA), on kindling and the antikindling action of stimulation of the LC. Stimulation of the LC during amygdaloid kindling increased the number of afterdischarges (ADs) spent in the early stages of partial seizure and decreased the number of ADs spent in later stages of generalized seizure, as has been described previously. LC-stimulated rats also displayed longer durations of AD during early stages of kindling. The antikindling effect of LC stimulation was blocked by lesions of the dorsal bundle, whereas the facilitatory effects of LC stimulation on generalization and on the duration of AD were unaffected by the lesions. These results suggest that the antikindling action of LC stimulation is mediated by the ascending projections of noradrenergic neurons, presumably through enhanced release of noradrenaline. On the other hand, the facilitatory effects of LC stimulation on the development of later stages of seizure and on the duration of AD appear to be independent of the ascending dorsal bundle.

Afferent Pathways↗
PubMed1989

Urethane anesthesia blocks the development and expression of kindled seizures.

The effect of anesthetic and subanesthetic doses of urethane on the development of amygdala kindled seizures and on the expression of previously kindled seizures was studied in hooded rats. An anesthetic dose of urethane (1.5 g/kg) almost completely eliminated evoked afterdischarge and completely eliminated convulsive behavior in both groups. It also eliminated the seizure response to pentylenetetrazol. Subanesthetic doses of urethane (0.25 and 0.5 g/kg) strongly attenuated the expression of previously kindled seizures. These results suggest that urethane may not be an appropriate anesthetic for the study of epileptiform phenomena.

Anesthesia, General↗
PubMed1988

Anterior neocortical kindling in vasopressin-deficient rats.

Kindling of seizures with stimulation of anterior neocortex was examined in control rats and in Brattleboro rats deficient in arginine-vasopressin (AVP). There were no significant differences between control rats, homozygous Brattleboro rats, and heterozygous Brattleboro rats in the rate and pattern of kindling of generalized seizures. Thus AVP is not critically involved in anterior neocortical kindling.

Animals↗