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Abstract
The kindling effect is described as involving a gradual change in behavior in response to periodic invariant electrical stimulation of specific brain sites, culminating in convulsions. Two premises are evaluated relative to kindling: (a) The kindling effect provides an excellent model of human epileptic conditions. (b) The amino acid taurine will act to suppress convulsions developed during kindling. Consideration of behavioral, electrophysiological, neurological, and chemical aspects of kindling suggest that behavioral aspects may model those of epilepsy, but it is probable that neurological mechanisms in some types of epilepsy are different from those underlying the kindling event. Although taurine appears to have an important role (e.g., as an inhibitory neurotransmitter) and has been successful in suppressing convulsions in humans and in some experimentally induced seizures, it has been found to have no effect on convulsions developed via kindling. (65 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
... The kindling effect has been investigated in a number of laboratories (e.g., Gaito, 1976;Goddard, McIntyre, & Leech, 1969;Wada & Sato, 1975). In rats, this effect involves a change from normal exploration (Stage 1) to behavioral automatisms (Stage 2, BA-chewing, eye closure on ipsilateral side, salivation) and finally to clonic convulsions (Stage 3, CC) in response to electrical stimulation of a specific brain site (e.g., amygdala). ...
... A permanent change that does not damage tissue is assumed to occur in the brain during kindling (Goddard et aI., 1969;Racine, 1978). Behavioral, chemical, electrophysiological, and neurological aspects of this effect have been investigated by many researchers (Gaito, 1976;Racine, 1978). ...
A number of exploratory experiments produced results that suggested a simplified method of producing suppression of kindled behavior by 1-Hz sine-wave stimulation. This method involved determining the effective threshold intensity to produce kindled behavior (ETI1), followed 1 h later by stimulation with 1-Hz sine waves at the ETI1 intensity for 5 min. Three hours later, a second 1-Hz trial occurred. Eighteen hours later, ETI2 was determined. Four experiments with this method indicated clearly its effectiveness. However, when contrasted with the previous method used (a 1-60-1 sequence over a number of days with an intertrial interval of 1 h) both methods were equally effective.
... It would be interesting to know whether there is some special plasticity of the telencephalon, measurable by ICSS rates. In addition to its possible relevance to other neuroplasticity phenomena, such as kindling (Gaito, 1976) and its relevance to the broad question of the neural substrates of learning, knowledge of a special changeability of the caudate nucleus might help in understanding the origins of dyskinesias that arise spontaneously or that result from chronic drug treatments (Yahr, 1976). Therefore, we replicated the early results in additional animals, some of which had electrodes implanted both at the telencephalic loci and also at more caudal points, i.e., lateral hypothalamus, substantia nigra, or midbrain reticular formation. ...
... Cooper and Taylor (1967) reported gradual increase in ICSS at points in periventricular gray over the first few sessions. Enhancement, to the extent of seizures, in responsiveness to electrical or cholinergic stimulation of telencephalic points, including caudate nucleus, is an outcome of studies of "kindling" (Gaito, 1976;Vosu & Wise, 1975). Telencephalic points appear particularly susceptible to epileptic activity during self-stimulation experiments (Routtenberg & Santos-Anderson, 1977). ...
Nine male Holtzman rats, each with electrodes implanted in a telencephalic region and 7 of them also with successful placements in a more caudal brain reward region, were taught to self-stimulate. Rates in the caudate nucleus and medial frontal cortex showed a gradual increase over daily sessions, but self-stimulation in lateral hypothalamus, substantia nigra, and reticular formation did not have this property. In the telencephalon, rates in the first 5 testing sessions were low, averaging 138 barpresses/10-min session. Intracranial self-stimulation (ICCS) rates gradually rose during approximately the next 15 sessions, leveling off at an average of 453/10 min. Seizures were sometimes observed as rates increased at telencephalic points. The possibilities are discussed that the plasticity in ICSS is related to the kindling phenomenon or to dyskinesias that result from chronic administration of drugs presumed to have their main locus of action in the corpus striatum. (16 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
... It also appears to bea transient event like the tran-sient interference ("after effect") described by McIntyre and Goddard (1973). These transient aspects were in sharp contrast to the kindling process which was relatively permanent (Gaito, 1976;Goddard, McIntyre, & Leech, 1969;Racine, 1978). ...
In two preceding papers (Gaito, 1985a, 1985b), I presented statistical data for two important variables in the suppression of kindling behavior (duration of stimulation and intertrial intervals). In this article, the relative contribution of each of these (plus other reliable variance components) is contrasted with the associated error components. In both cases, reliable variance contributed a substantial proportion of the overall variance, whereas lesser amounts of variance were associated with error components when suppression was complete. The overall results suggest that the suppression process is a transient time-dependent one whose magnitude decreases with short durations of stimulation and with long intertrial intervals.
... Repeated low-level electrical stimulation of any of a number of brain regions induces progressive changes which culminate in clonic convulsions; as stimulation trials proceed, the animal's behavior changes in a gradual and predictable way from an initial stage of exploratory behavior (Stage 1), to behavioral automatisms usually involving facial contractions, chewing movements, eye closure, and salivation (Stage 2-BA), and, finally, to a clonic convulsion (Stage 3-CC). Some researchers have extended this classification to more stages by expansion of Stages 2 and 3 (Racine, 1972)" Behavioral, chemical, electrophysiological, and neurological aspects of this effect have been investigated by many researchers (Gaito, 1976;Racine, 1978). ...
Three experiments were conducted to evaluate the effect of 1-Hz brain stimulation of the amygdala on kindling behavior induced by 60-Hz sine-wave stimulation in the contralateral amygdala. In Experiment 1, the effective threshold intensity (ETI) to elicit a kindled response with 60-Hz stimulation was determined on four separate occasions with 15 trials between determinations (three per day) for each of three groups. Experimental rats in Group 1 were stimulated with 1-Hz sine waves in one amygdala, then with 60-Hz current in the opposite amygdala, followed by 1-Hz stimulation of the first site (1-60-1, OA), with 1-h interstimulation intervals. Group 2 was treated with the 1-60-1 pattern, but with all stimulation in the same amygdala (1-60-1, SA). Group 3 received only the 60-Hz stimulation trials (X-60-X), on the second trial. Group 2 showed the typical suppression result, a gradual increase in threshold over the four ETI determinations. However, Group 1’s responses were similar to those of Group 3: ETI values decreased gradually over the determinations. Later, when Group 1 received a set of trials in which 1- and 60-Hz current stimulation was to the same site, suppression responses occurred. Two further experiments were conducted with similar results. These results suggest that the suppression effect generated by 1-Hz stimulation appears to involve a local process, an intrahemispheric effect.
... During kindling, a permanent change that does not damage tissue is assumed to occur in the brain. Behavioral, chemical, electrophysiological, and neurological aspects of this effect have been investigated by many researchers (Gaito, 1976 ;Racine, 1978). ...
Experiments were conducted to evaluate the effect of 5-day and 14-day intertrial intervals of 1-Hz brain stimulation on kindling behavior induced by 60-Hz sine-wave stimulation. The effective threshold intensity (ETI) to elicit a kindled response with 60-Hz stimulation was determined on two separate occasions with 15 brain-stimulation trials between determinations. In Experiment 1, experimental rats were stimulated with 1-Hz sine waves before and after a 60-Hz brain-stimulation trial, with a 14-day interval between each stimulation session (Group 1- 60-1). A second group (Group X-60-X) received only the 60-Hz stimulation on the same trials as those on which Group 1-60-1 was stimulated with 60-Hz current. Experiment 2 was similar to Experiment 1, but the interval was 5 days. In previous experiments with 1, 3, or 24 h between trials, Group 1-60-1 had had a gradual increase in the intensity required to elicit a kindled response with 60-Hz current from ETI1 to ETI4 (the suppression effect). However, with a 72-h interval, a decline similar to that of Group X-60-X occurred in ETI values. The results with 14-day and 5-day intervals were similar to those with a 72-h interval. Suppression of kindled behavior on daily trials was not present in Group 1-60-1, in contrast to the results with 1, 3, and 24 h. Apparently, intervals of 3 days or greater allow much of the suppression effect to dissipate.
... Na€ ıve animals were used to avoid the confounding, kindling effect that previous seizures may have on LS during subsequent exposures (Gaito 1976;McNamara et al. 1985;Pilla et al. 2012). ...
Tonic–clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (−42, −49, and −57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (−60, −86, and −73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (−0.4 ± 1.5 g) or FB (−1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males.
... Naïve animals were used for each exposure because we previously found that animals exhibit decreased LS times as a function of increasing numbers of HBO 2 -induced seizure (Pilla et al., 2012a). This is similar to the kindling effect that is commonly described in epilepsy literature (Gaito, 1976, Racine, 1978, McNamara et al., 1980. The highest dose selected was 320 mg/Kg of body weight, which is equivalent to the half of the LD 50 for PSE reported for rat (Pfizer, 2007). ...
Pseudoephedrine (PSE) salts (hydrochloride and sulfate) are commonly used as nasal and paranasal decongestants by scuba divers. Anecdotal reports from the Divers Alert Network (DAN) suggest that taking PSE prior to diving while breathing pure O2 increases the risk for CNS oxygen toxicity (CNS-OT), which manifests as seizures. We hypothesized that high doses of PSE reduce the latency time to seizure (LS) in unanesthetized rats breathing 5 atmospheres absolute (ATA) of hyperbaric oxygen. Sixty-three male rats were implanted with radio-transmitters that recorded electroencephalogram (EEG) activity and body temperature (TB). After ⩾7 day recovery, and 2hr before "diving", each rat was administered either saline solution (control) or PSE hydrochloride intragastrically at the following doses (mg PSE/Kg): 0, 40, 80, 100, 120, 160, and 320. Rats breathed pure O2 and were dived to 5 ATA until the onset of behavioral seizures coincident with neurological seizures. LS was the time elapsed between reaching 5 ATA and exhibiting seizures. We observed a significant dose dependent decrease in the LS at doses of 100-320 mg/Kg, whereas no significant differences in LS from control value were observed at doses ⩽80 mg/Kg. Our findings showed that high doses of PSE accelerate onset of CNS-OT seizures in unanesthetized rats breathing 5 ATA of poikilocapnic hyperoxia. Extrapolating to humans, we conclude that the recommended daily dose of PSE should not be abused prior to diving with oxygen-enriched gas mixes or pure O2.
... During stage 3 behavior, the rat stands on its hind paws and bilateral convulsions of the forelimbs occur. Behavioral, chemical, electrophysiological, and neurological aspects of this effect have been investigated by many researchers (Gaito, 1976a;Racine, 1978). ...
An experiment was conducted to evaluate the effect of various frequencies of brain stimulation on kindling behavior induced by 60-Hz sine wave stimulation. The effective threshold intensity (ETI) to elicit a convulsion was determined on four separate occasions with 5 days of daily trials between determinations. On each day experimental rats were stimulated with current of a specific frequency on the first and third trials for 60 seconds duration and with 60-Hz current for 30 seconds on the second trial (one hour intertrial interval). There were five experimental groups, one each for 1, 5, 10, 30, and 60-Hz stimulation. A sixth group received no stimulation on trials 1 and 3 and 60-Hz current on trial 2. Suppressor of convulsive behavior induced by the 60-Hz stimulation trial was present for all ETI determinations with 1-Hz and 5-Hz stimulation; the mean ETI increased on each successive determination. Suppression was prominent also for the 10-Hz group until the ETI4 determination. Suppression was moderate for the 30-Hz and 60-Hz groups. Overall, it appeared that the interference effect gradually increased with remoteness from the 60-Hz point.
... During Stage 3 behavior, the rat stands on its hind paws and bilateral convulsions of the forelimbs occur. Behavioral, chemical, electrophysiological, and neurological aspects of this effect have been investigated by many researchers (Gaito, 1976a;Racine, 1978). ...
Experiments were conducted to evaluate the effect of two intertrial intervals of 1-Hz brain stimulation on kindling behavior induced by 60Hz sine wave stimulation. In two experiments, the effective threshold intensity (ETI) to elicit a convulsion was determined on four separate occasions with 5 days of daily trials between determinations. On each day experimental rats were stimulated with 1-Hz current on the first and third trials for 120 seconds duration and with 60-Hz current for 30 seconds on the second trial (1-60-1 group). A second group was stimulated with 60-Hz-current on each trial (60-60-60 group). A third group received no stimulation on Trials 1 and 3 and 60-Hz current on Trial 2 (X-60-X group). In Experiment 1, the intertrial interval was 3 hours; a 24 hour interval was used in Experiment 2. The results were similar in both experiments. For the 1-60-1 group, there was a steady increase in the intensity required to elicit a convulsion shown with 60-Hz current from EtI1 to ETI4. However, the 24 hour interval produced a lesser effect than did 3 hour interval (or the 1 hour interval used in previous experiments). Rats in the other groups maintained relatively stable values from ETI1 to ETI1, with a slight decline occurring. Suppression of convulsive behaviour on daily trials was present with the 1-60-1 groups, and nonexistent with the other groups.
... A permanent change that does not damage tissue is assumed to occur in the brain during kindling (Goddard et al., 1969;Racine, 1978). Behavioral, chemical, electrophysiological, and neurological aspects of this effect have been investigated previously (Gaito, 1976a;Racine, 1978). ...
An experiment was conducted to evaluate the effect of 1-Hz or direct current brain stimulation on kindling behavior induced by 60-Hz sine wave stimulation. The effective threshold intensity to elicit a convulsion was determined on four separate occasions with 5 days of daily trials between determinations. On each day one group of experimental rats was stimulated with 1-Hz sine wave current before and after stimulation with 60-Hz sine wave current (1-60-1 group). Another group received direct current stimulation and 60-Hz current (D-60-D group). A third group received only 60-Hz stimulation. Suppression of kindling behaviour usually induced by the 60-Hz stimulation occurred with 1-Hz stimulation; the mean threshold value increased on each successive determination. Suppression was most pronounced for the direct current group; it appeared after a single trial and persisted for 32 days after the last threshold determination. In contrast, most of the rats in the 1-60-1 group had recovered from the suppression after the 32 day period of nonstimulation. A second phase of the experiment indicated that the increase in threshold values for the D-60-D group occurred after a single DC stimulation. These results are consistent with the hypothesis generated by previous research that suppression following 1-Hz stimulation is not due to tissue damage.
... Kindling is a model of epilepotogenesis (Gaito, 1976;Goddard, 1967;McIntyre et al., 2002;Mody and MacDonald, 1995;Racine, 1978;Weiss et al., 1995) where the term was first proposed by Goddard and colleagues who performed much of the early work (Goddard, 1967). Epileptogenesis is a set of progressive neurochemical, neuroanatomical, and neurophysiological changes that lead to spontaneous recurrent seizures (Stables et al., 2002). ...
Long-term potentiation (LTP) of synaptic transmission is a widely accepted model that attempts to link synaptic plasticity with memory. LTP models are also now used in order to test how a variety of neurological disorders might affect synaptic plasticity. Interestingly, electrical stimulation protocols that induce LTP appear to display different efficiencies and importantly, some may not be as physiologically relevant as others. In spite of advancements in our understanding of these differences, many types of LTP inducing protocols are still widely used. In addition, in some cases electrical stimulation leads to normal biological phenomena, such as putative memory encoding and in other cases electrical stimulation triggers pathological phenomena, such as epileptic seizures. Kindling, a model of epileptogenesis involving repeated electrical stimulation, leads to seizure activity and has also been thought of, and studied as, a form of long-term neural plasticity and memory. Furthermore, some investigators now use electrical stimulation in order to reduce aspects of seizure activity. In this review, we compare in vitro and in vivo electrical stimulation protocols employed in the hippocampal formation that are utilized in models of synaptic plasticity or neuronal hyperexcitability. Here the effectiveness and physiological relevance of these electrical stimulation protocols are examined in situations involving memory encoding (e.g., LTP/LTD) and epileptiform activity.
Nach dem bisherigen Kenntnisstand ist bei Berücksichtigung von Kontraindikationen die transkranielle magnetische Kortexstimulation mit Einzelreizen als ein sicheres und nebenwirkungsfreies Untersuchungsverfahren anzusehen. Die bei der Stimulation auftretende Energieübertragung auf das Gehirn ist vernachlässigbar gering, biologische Effekte, wie z. B. die Zunahme der zerebralen Blutperfusion, liegen im physiologischen Bereich. Transiente Veränderungen höherer Hirnfunktionen können auftreten und möglicherweise genutzt werden, um z. B. die sprachdominante Hemisphäre zu identifizieren. Wegen mechanischer Effekte dürfen sich in der Nähe der Stimulatorspule weder inner-noch außerhalb des Körpers der untersuchten Probanden stark leitfähige Objekte mit einer größeren Querschnittsfläche befinden. Patienten mit Epilepsie, Anfallsbereitschaft, frischem Herzinfarkt, Herzrhythmusstörungen oder Herzschrittmacher sollten nicht untersucht werden. Mögliche Gefährdungen durch ausgelöste starke Muskelkontraktionen sollten berücksichtigt werden (z. B. Wurzelstimulation bei instabiler Wirbelsäulenfraktur). Hörgeräte sollten vor der Untersuchung entfernt werden. Für die transkranielle elektrische Hirnstimulation gelten Frakturen oder Fissuren des Schädels als zusätzliche Kontraindikationen.
An experiment was conducted to evaluate the effect on kindling behavior of stimulation with 1-Hz current prior to 60-Hz sine-wave stimulation. In the first phase, one group of rats had 30 trials of 1-Hz sine waves, 3 trials/day, 1 h between trials (1-60 group), and then received 30 kindling trials over 10 days. A second group had no stimulation on the initial trials (X-60 group) prior to 30 kindling trials. In a second phase, two other groups were treated in a similar fashion, but after a delay of 30 days. The results were the same in both phases: The 1–60 group showed retarded kindling behavior.
Experiments were conducted to evaluate the effect of various durations of 3-Hz brain stimulation on kindling behavior induced by 60-Hz sine-wave stimulation of the amygdala. In two experiments the effective threshold intensity (ETI) to elicit a convulsion was determined on four separate occasions with 5 days of daily trials interspersed between determinations. On each day experimental rats were stimulated with 3-Hz current on the first and third trials for 5, 15, 30, 60, 120, or 300 sec duration and with 60-Hz current for 30 sec on the second trial. A steady increase in the intensity required to elicit a convulsion with 60-Hz current from ETI1 to ETI4 resulted for all rats with durations of 15 sec or greater. Rats stimulated only with 60-Hz sine waves and those in the 5-sec group maintained relatively stable values from ETI1 to ETI4, with a slight decline occurring. Suppression of the expected 60-Hz-induced convulsive behavior on daily trials was modest in the 15-sec group, pronounced with the 30-sec group, and drastic with the other groups. The 300-sec group had the greatest suppressive effect operating. The suppression effect appeared not to be due to tissues damage inasmuch as many of the experimental rats (except the 300-sec group) convulsed again at previous low ETI levels following a 16-day rest at the end of the experiment. This result suggests that the suppression effect is a relatively transient event.
Two experiments were conducted to evaluate the effect on kindling behavior of stimulation with 1-Hz current prior to 60-Hz sine-wave stimulation. In both experiments one group of rats had 30 trials of 1-Hz sine waves, 3 trials/day, 1 h between trials (1–60 group), and then received 30 kindling trials over 10 days. A second group had no stimulation on the initial trials (X-60 group) prior to 30 kindling trials. The 1–60 group showed retarded kindling behavior in both experiments.
Data from a number of sequential alternation experiments were factor analyzed to determine the number of common factors present. Three dependent variables (latency of convulsion, number of trials to six convulsions, duration of convulsions) were evaluated by three procedures: principal components solution with 1s in main diagonals, principal axes solution with largest r in the diagonals, principal axes solution with R2 in the diagonals. The results were similar; the presence of two factors was suggested in the latency and criterion measures (primary site stimulation and secondary site stimulation) and one in the duration data. A principal components factor analysis over the three dependent variables showed the presence of three factors, those observed in each of the separate analyses.
These experiments investigated the effect of 3- Hz brain stimulation on behavior induced by 60- Hz stimulation.
These exploratory experiments investigated the effect of 3-Hz brain stimulation on behavior induced by 60-Hz brain stimulation when the former was presented simultaneously with, or following, the latter. In the simultaneous case, 3-Hz stimulation to one amygdala and 60 Hz to the other produced a slower kindling rate than did bilateral stimulation with 60 Hz. When 3-Hz stimulation followed six convulsion trials of 60-Hz stimulation, there was no effect on the convulsive tendency; however, with rats in which the convulsive pattern was relatively stable and 48 or more convulsive trials were followed by 24 trials of 3-Hz stimulation at double intensity or 36 trials at the same intensity as previous 60-Hz stimulation, a reversal effect was observed, that is, a return to nonconvulsive behavior.
There are three types of interference effects during kindling: that produced by alternate stimulation of homologous brain sites, by successive stimulation of one site, and by stimulation of one site by different frequencies. These three types of interference appear to be similar. Facilitation and interference effects during kindling seem to be generated by the operation of two factors: a “neurological trace” process, possibly involving synaptic changes, and an “aftereffect.” The latter process may be the main basis for these interference effects.
An experiment was conducted with rats to evaluate the effect of various low frequencies of brain stimulation on kindling behavior induced by 60-Hz sine-wave stimulation. The effective threshold intensity (ETI) to elicit altered behavior was determined on four separate occasions, with 5 days of daily trials between determinations. On each day, experimental rats were stimulated with current of a specific frequency on the first and third trials and with 60-Hz current on the second trial. There were four experimental groups, one each for 1-, .1-, .01-, and .001-Hz stimulation. A fifth group received no stimulation on Trials 1 and 3 and 60-Hz current on Trial 2. Suppression of altered behavior induced by the 60-Hz stimulation trial was present for all ETI determinations with the four experimental groups; the mean threshold increased on each successive determination. Suppression was greatest for the .1, .01, and .001 groups. Grossly, it appears that the interference effect gradually increases with decreasing frequency.
The use of 1- or 3-Hz brain stimulation has been effective in eliminating or preventing kindling behavior produced by 60-Hz stimulation. In this paper, statistical data are presented on the effects of duration of stimulation on suppressing this kindling behavior. For experimental rats, each daily experiment involved the sandwiching of the kindling-producing agent (60-Hz sine wave stimulation) between trials of the suppression-producing agent (1-Hz or 3-Hz sine waves) (i.e., a sequence of 1-60-1 or 3-60-3). The durations used were 0 (control), 5, 15, 30, 60, 120, 180, 300, and 600 sec. In general, the degree of suppression increased with increasing duration of stimulation. Recovery from suppression following 15 or 16 days of nonstimulation decreased with increasing durations. Complete, or near complete, recovery resulted with durations of 60 sec or less; however, there was some recovery in all groups.
Previous research indicated that an oscillation effect resulted during sequential alternation of unilateral amygdaloid stimulation with consistent low-latency values for one side and consistent high values for the contralateral one. In this study only one trial of stimulation was applied before alternating to the opposite side. The oscillation tendency resulted under this condition in a similar fashion as in previous studies in which stimulation was continued with one side until six convulsions occurred.
An experiment was conducted to evaluate the effect of a 72-h intertrial interval of 1-Hz brain stimulation on kindling behavior induced by 60-Hz sine-wave stimulation. The effective threshold intensity (ETI) to elicit a kindled response with 60-Hz stimulation was determined on four separate occasions with 15 trials between determinations. Experimental rats were stimulated with 1-Hz sine waves before and after a 60-Hz brain stimulation trial with a 72-h interval between stimulation sessions (1-60-1 group). A second group received only the 60-Hz stimulation on the same trials as those on which the 1-60-1 group was stimulated with 60-Hz current (X-60-X group). In previous experiments with 1, 3, or 24 h between trials, the 1-60-1 group had a gradual increase in the intensity required to elicit a kindled response with 60-Hz current from ETI1 to ETI4 (the suppression effect). However, the 72-h interval produced a decline in ETI values similar to that of the X-60-X group, but not as great. Suppression of kindled behavior on daily trials was not present for the 1-60-1 group, in contrast to results of previous experiments. Apparently, the 72-h interval allowed much of the suppression effect to dissipate.
Data from a number of sequential alternation experiments for 125 subjects were factor analyzed to determine the number of common factors present. Three measures (mean latency of convulsion, mean number of trials to, six convulsions, mean duration of convulsions) were evaluated by principal components analyses. The presence of two factors was suggested in the latency, criterion, and duration measures (primary site stimulation, secondary site stimulation). The two factors were more clearly defined for the latency data than for the other measures. Further analyses with individual trials (rather than means) for the 125 subjects provided approximately the same results. Factor analyses of data from 35 rats stimulated only on one side showed the presence of one factor in all analyses. These results suggest a two-factor interpretation of kindling events, possibly the two effects of Goddard et al. and McIntyre and Goddard: a long-term neurological circuitry modification for each of the primary and secondary sites and a short-term aftereffect which accounts for the negative-transfer aspects from the primary to the secondary site.
Previous research had indicated that an oscillation effect resulted during sequential alternation of unilateral amygdaloid stimulation with consistently low latency values for one side and consistently high values for the contralateral one. The effect of intensities approximately 15 microA above threshold was investigated in this study. The oscillation tendency occurred at these near-threshold intensities both for rats which previously had shown oscillation patterns at different intensities and for those which were being stimulated for the first time.
Data from a number of kindling experiments involving 60 convulsion trials were evaluated by a truncated principal components factor analysis to determine the number of common factors present. These data were obtained on 123 rats in which periodic low-intensity unilateral stimulation was alternated from one amygdala to the other after six convulsions on each side. Two dependent variables (latency of convulsion, duration of convulsion) were analyzed over Trials 1–60, 1–24, 25–60, 1–12, 13–24, 25–36, 37–48, and 49–60 for each dependent variable. Two factors appeared for all latency analyses: primary site stimulation (first side stimulated), secondary site stimulation (second side stimulated). The factor resolution was not clear for the duration measure; two to four factors were suggested in the various analyses.
Previous research with the kindling paradigm indicated that an oscillation effect resulted during sequential alternation of unilateral amygdaloid stimulation with consistently low values for one side and consistently high values for the contralateral one. The effect of interphase intervals of 1 and 14 days following (Experiment 1) and during (Experiment 2) the development of oscillation was investigated in this study. In Experiment 1 both the 1-day and 14-day intervals disrupted the oscillation tendency in criterion data but not in the latency measure. In Experiment 2 disruption of oscillation occurred only for the criterion measure in the 14-day group.
In 2 experiments, a total of 25 aged Wistar male rats (approximately 420-475 days old) were subjected to stimulation of each amygdala in an alternating sequence. Their behavioral response to this stimulation was similar to that found previously with younger rats, systematically going from normal exploration, to automatic behavior, to clonic convulsions. Results also show the "oscillation effect," i.e., low values in latency when stimulated on one side and high values when stimulated on the opposite side. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The effect of agents enhancing or diminishing serotonergic activity on seizures kindled from the rabbit amygdala was examined. Acute administration of 5-hydroxytryptophan (5-HTP) 10 and 25 mg/kg (administered in combination with a peripheral decarboxylase inhibitor), quipazine 1, 5 and 10 mg/kg or femoxetine 5 and 15 mg/kg which enhance serotonergic activity affected neither the intensity of behavioral seizures nor the duration of bioelectrical ones. 5-HTP 25 mg/kg and femoxetine 15 mg/kg prolonged the duration of behavioral seizures. Chronic administration of 5-HTP 25 mg/kg and femoxetine 15 mg/kg prolonged the duration of behavioral seizures. Chronic administration of 5-HTP 25 mg/kg had no effect on the development of kindled seizures. Acute administration of p-chlorphenylalanine (PCPA) 250 mg/kg reduced the intensity and shortened the duration of behavioral seizures. Cyproheptadine which blocks the postsynaptic action of serotonin shortened the duration of behavioral seizures. Chronic administration of PCPA 80 mg/kg delayed the development of kindled seizures. It is concluded that a pharmacological stimulation of the serotonergic system exerts no or little enhancing effect, whereas pharmacological inhibition of this system attenuates and delays the development of seizures kindled from the rabbit amygdala.
Since the development of the kindling preparation there has been much speculation on the contribution of conditioning mechanisms in accounting for the phenomenon. Two recent reports have described attempts to establish conditioned responses utilizing the kindling model. We suggest that the conclusion of uncondition-ability asserted by Wyler & Heavner (1979) is not warranted because of serious misunderstandings relating to the concepts and techniques that are central to both neurophysiological and conditioning theory. We further suggest that the results of their retardation effect can be better interpreted as positive evidence for the successful establishment of conditioning. With respect to the findings by Janowsky et al. (1980), we regard their sample size (2 animals undergoing simultaneous kindling and conditioning and one animal beginning conditioning following kindling) as inadequate for a conclusive demonstration of the success they report. Both studies, however, are seen as substantive contributions, insofar as they introduce this important perspective in kindling research, that can be expected to occupy a major role in the future developments of basic and clinical epileptology.
Male Long-Evans rats were stereotaxically implanted bilaterally with bipolar electrodes in the central amygdala. Rats were then kindled once daily for 1 sec until 3 consecutive Stage V [25] kindled seizures were elicited. On the following day, animals were injected (IP) with either saline, naloxone (10 mg/kg), naltrexone (10mg/kg) or morphine sulfate (10 mg/kg) and again stimulated at the kindling stimulation parameters. Saline injected animals continued to show long bilateral AD's and behaviors (i.e., forelimb clonus, rearing, falling) typical of Stage V kindled animals. In contrast, rats injected with naloxone or naltrexone showed reduced behavioral seizures. Potentiation of post-ictal spiking by morphine in amygdaloid-kindled rats was also observed supporting previous reports [7,21]. In a second experiment, the reduction of kindled seizure serverity by naloxone was systematically replicated. It is concluded that opiates can significantly modify amygdaloid-kindled seizures, and that brain endorphins may play a role in the development or maintenance of an amygdaloid-kindled seizure focus.
Experiments were conducted to evaluate the effect of 3 Hz brain stimulation on kindling behavior induced by 60 Hz sine waves stimulation. In Experiment 1,12 rats were subjected to 40 or 60 convulsion trials with 60 Hz stimulation and then given 36 trials of 3 Hz stimulation. Whe'n these rats were stimulated again with 60 Hz sine wave current at the same brain site, none of the rats showed a convulsion in nine test trials. The intensity of stimulation had to be increased on test trial 10 to elicit convulsions for each rat. Of 10 rats in two control groups, only 1 did not convulse during the nine test trials. In Experiment 2 the effective threshold intensity (ETI) to elicit a convulsion was determined on five separate occasions with 10 days of daily trials between determinations. On each day experimental rats were stimulated with 3 Hz current on the first and third trials and with 60 Hz current on the second trial (3–60‐3 group). A steady increase in the intensity required to elicit a convulsion with 60 Hz current from ETI, to ETI 5 resulted. Rats stimulated only with 60 Hz sine waves on the second trial each day (X‐60‐X group) maintained relatively stable values from ETI, to ETI 5 . In the four, 10‐day blocks of trials, convulsions were suppressed in 20% to 80% of the trials over the 10 day period for the 3–60‐3 group, with the greatest effect occurring after about 4 days of stimulation. This suppressive effect was prominent both with rats that were at the convulsion stage prior to the first application of 3 Hz stimulation and with rats that were at preconvulsion stages. In Experiment 3 the permanency of the suppressive effect was evaluated. Eight suppressed rats from the experimental group in Experiment 2 and 4 control rats were stimulated for 90 trials over 30 days with 60 Hz current, and ETI values were determined after each set of six trials. Four of the 8 experimental rats were convulsing at ETI,. within 20 days.
RÉSUMÉ
Des expériences ont été réalises afin d'évaluer les effets d'une stimulation cArébrale à 3 Hz sur l'effet d'embrasement obtenu par une stimulation sinusoïdale à 60 Hz. Dans la première série expérimentale, 12 rats ont été stimulés 40 à 60 fois avec une fréquence de 60 Hz capable d'induire des convulsions, puis 36 fois avec une fréquence de 3 Hz. Lorsque ces rats ont étéà nouveau stimulés, au niveau de la même structure cérébrale, avec un courant sinusoïdal à 60 Hz, aucun d'eux n'a présenté de convulsions au cours des 9 stimulations tests suivantes. l'intensité de la stimulation a dûêtre augmentée au cours de la dixième stimulation test pour que survienne une convulsion chez chacun des rats. Parmi les 10 rats de deux groupes de contrôle, un seul d'entre eux n'a pas convulsé pendant les 9 stimulations tests. Dans la deuxième série expérimentale, l'intensité seuil efficace (ISE) pour induire une convulsion a étéévaluée de façon précise à cinq occasions différentes. Ces évaluations précises ont été effectuées a 10 jours d'interfalle pendant des périodes où l'animal était stimulé tous les jours. Chaque jour les rats d'expériences étaient stimulés avec un courant à 3 Hz la première et la troisième fois et avec un courant à 60 Hz la seconde fois (groupe 3–60‐3). II en est résulté une augmentation stable de l'intensité du courant à 60 Hz nécessaire pour induire une convulsion en allant de ISE, à ISE 5 . Les rats qui ont été seulement stimulés chaque jour avec un courant sinusoïdal à 60 Hz ont gardé, lors de laseconde stimulation (groupe 3‐60‐3), des valeurs relativement stables en allant de ISE, à ISE,. Dans les quatre séries de 10 jours, au cours desquelles l'animal était stimulé journellement, les convulsions étaient supprimées entre 20 et 80% des fois, lorsqu'il était stimulé selon le protocole du groupe 3–60‐3 pendant 10 jours; l'effet le plus important s'est fait sentir après environ 4 jours de stimulation. Cet effet suppressif était plus important aussi bien chez les rats qui avaient atteint le stade de la convulsion avant l'application de la première stimulation à 3 Hz que chez ceux qui n'étaient encore qu'au stade préconvulsif, lorsque celle‐ci a commencéàêtre appliquée. Dans la troisième série expérimentale, la durée de cet effet suppressif a étéévaluée. 8 rats de la série expérimentale 2, chez lesquels les convulsions avaient été supprimées, et 4 rats contrôles ont été stimulés avec un courant à 60 Hz 90 fois pendant 30 jours; les valeurs d'ISE ont étéétablies de façon précise après chaque série de 6 stimulations. 4 des 8 rats expérimentaux ont convulsé dans les 20 jours au cours de ISE 1
RESUMEN
Se han realizado experimentos para valorar el efecto de la estimulación cerebral (3‐Hz)sobre el comportamiento inducido (Kindling) con estimulación cerebral de onda sinusal de 60‐Hz. En el Experimento I, 12 ratas fueron sometidas a 40 o 60 ensayos convulsivos con estimulación de 60‐Hz y, posteriormente, se añadieron 36 ensayos con estimulación de 3‐Hz. Cuando estas ratas fueron estimuladas nuevamente con corriente de ondas sinusales de 60‐Hz en el mismo lugar cerebral, ninguna mostró convulsiones en nueve ensayos. Fue necesario un aumento de la intensidad de la estimulación en el ensayo 10 para detectar una convulsitin en cada rata. Solamente una rata no convulsionó de 10 ratas en dos grupos control durante nueve ensayos. En el Experimento 2 el umbral de la intensidad efectiva (ETI) para producir una convulsión se determineó en cinco ocasiones distintas durante 10 dias de ensayos diarios entre las determinaciones. Las ratas fueron estimuladas diariamente con corriente de 3‐Hz en el primer y tercer ensayo y con corriente de 60‐Hz en el segundo ensayo (grupo 3–60‐3). En estas condiciones se necesitó un aumento continuo en la intensidad requerida para producir una convulsión con corriente de 60‐Hz desde ETI 1 a ETI 5 Las ratas que solo se estimularon con ondas sinusales de 60‐Hz en el segundo ensayo de cada dia (grupo X‐60‐X) mantuvieron unos niveles relativamente estables desde ETI 1 , a ETI 5 . En los cuatro bloques de diez dias de ensayos se consiguió una supresión de las convulsiones en un 20 a un 80% de los ensayos durante el periodo de diez dias para el grupo 3–60‐3 con el mayor efecto a partir del cuarto dia de estimulación. Este efecto supresor fue prominente en las ratas que estaban en estado con‐vulsivo previo a la primera aplicación de la estimulación de 3Hz y tambien en las ratas que permanecian en periodos preconvulsivos. En el Experimento 3 sevaloró la persistencia del efecto supresor. Ocho ratas suprimidas pertenecientes al grupo experimental en el Experimento 2 y cuatro ratas control fueron estimuladas para 90 ensayos durante más de 30 dias con corriente de 60‐Hz determineándose los valores de ETI tras cada grupo de 6 ensayos. Cuatro de las ratas experimentales convulsionaron a ETI 1 , en un plazo de 20 dias.
A single stimulus applied once daily to the limbic system commonly leads to convulsive seizures yet seizures are relatively infrequent during intracranial self-stimulation (ICSS), a procedure that involves many hundreds of similar stimuli. The present study examined the possible role of electrode site, interstimulus interval, afterdischarge and reinforcement thresholds and postictal refractoriness in accounting for this paradox. Electrode location was an overriding factor: seizures were never seen with hypothalamic implants posterior to the level of the ventromedial nucleus but were elicited by the majority of more rostral reward sites. Frequent repeated stimulation by ICSS did not in itself prevent subsequent kindling or reverse the effects of earlier kindling; on the contrary, seizures induced by ICSS showed a progressive increase in severity similar to the progression produced by conventional kindling. Individual convulsive seizures, as in previous studies, conferred transient protection against further seizures whether from ICSS or from kindling. More prolonged protection occassionally developed after repeated convulsive seizures: protection was accompanied by continuous EEG slow-waves corresponding in presentation to clinical petit mal status. Prolonged resistance to seizures has also been reported after tonic-clonic status epilepticus causing temporal lobe damage. The relative infrequency of seizures during ICSS ordinarily appears to depend on the siting of the electrodes, on distinct short- and long-term postictal refractory states, and on the rat learning to restrict stimulus input to subseizural levels.
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