Electroconvulsive Shock Seizures Research Articles

Effects of repeated electroconvulsive shock seizures and pilocarpine-induced status epilepticus on emotional behavior in the rat

Affective symptoms are frequently observed in patients with epilepsy. Although the etiology of these behavioral complications remains unknown, it is possible that brain damage associated with frequent or prolonged seizures may contribute to their development. To address this issue, we examined the behavioral sequelae of repeated brief seizures evoked by electroconvulsive shock (ECS) and compared them with those resulting from prolonged status epilepticus (SE) induced with pilocarpine. Using the open-field and elevated plus-maze tests, we detected the presence of behavioral alterations indicative of elevated levels of anxiety in rats that were administered a course of ECS seizures. Fear conditioning was also enhanced in these animals. However, the rats that had experienced SE exhibited less anxiety-like behavior than controls and were severely impaired in fear conditioning. These results support the notion that brain lesions caused by either brief repeated seizures or SE is sufficient to induce some affective disturbances.

Synaptic alterations in the dentate gyrus molecular layer after repeated administration of electroconvulsive shock seizures

Synaptic alterations in the dentate gyrus molecular layer after repeated administration of electroconvulsive shock seizures

The effect of electroconvulsive shock seizures on behaviour induced by dopaminergic agonists and on immobility in the Porsolt test

Male, Wistar rats were given a course of eight electroconvulsive shock seizures (ECS group) or matched handling (control group). They were then tested for locomotion and rearing (7 days post-ECS), for grooming and yawning (9 days post-ECS), and for immobility in the Porsolt test (7, 14 and 21 days post-ECS). Seven days post-seizure, the ECS group showed significantly more locomotion following intraperitoneal administration of apomorphine (0.2 mg/kg), but not following injections of amphetamine (1 mg/kg). Drug-induced rearing was not different in the ECS and control animals. Nine days post-seizure, the ECS group showed significantly more grooming induced by the D-1 dopamine receptor agonist, SKF 38393 (1 mg/kg), but no difference in the yawning induced by the D-2 dopamine receptor agonist, quinpirole (0.05 mg/kg). In the Porsolt test, immobility was decreased in the ECS animals at 7 and 14, but not at 21 days post-ECS. It is concluded that ECS increases activity in the dopaminergic systems of the rat brain for at least 1–2 weeks post-seizure. The beneficial effects of electroconvulsive therapy (ECT) may relate to these dopaminergic alterations.

Spectral EEG effects of electroconvulsive shock stimulus parameters: the development of a rationale for the optimization of the ECT stimulus.

Electroconvulsive therapy (ECT) stimulus parameters, such as pulse amplitude, pulse width, pulse frequency, and stimulus duration, differently influence seizure threshold and, possibly, other neurobiological effects of ECT. We examined the influence of these parameters on the EEG power spectrum in an animal model. Adult, male, Wistar rats (n=54) were randomized to receive one of five differently constituted (approximately) 30-mC electroconvulsive shock (ECS) stimuli administered once on alternate days for a total of three ECS. A single-lead, unipolar EEG recording was obtained before, during, and immediately after each ECS seizure. EEG power was computed in eight frequency bands from 2 to 40 Hz. Greater ictal EEG power, greater postictal EEG suppression, and greater interictal EEG power, especially in lower frequency bands, were a priori defined as proxies of seizure efficacy. Motor and EEG seizure duration and a proxy for seizure generalization did not differ significantly across the five stimulus groups. Despite equivalent charge, the five stimuli varied widely in their effects on the EEG proxies of seizure efficacy. The narrow (0.6 milliseconds) pulse width, high (100 Hz) pulse frequency combination was best associated with EEG proxies of seizure efficacy; with this combination, a longer stimulus train duration appeared superior to a greater pulse amplitude. The wide (2 milliseconds) pulse and low (30 Hz) frequency combination was least associated with EEG proxies of efficacy. Stimulus "on" time, number of pulses delivered, and the rate of delivery of charge were not associated with the EEG proxies; the former finding questions the validity of dosing ECT in units of charge. These findings suggest a rationale for optimizing stimulus parameter choices during ECT and provide a framework for the evaluation of electrical aspects of the ECT stimulus.

Selective loss of hilar neurons and impairment of initial learning in rats after repeated administration of electroconvulsive shock seizures.

Prolonged seizures induced by neurotoxins or intracranial electrical stimulation provoke death of hippocampal neurons, which results in conspicuous learning and memory deficits. We examined whether repeated brief seizures elicited by electroconvulsive shock (ECS) can also deteriorate hippocampal structure and function. Adult Wistar rats were administered six ECS seizures, the first five of which were 24 h apart, whilst the last two were spaced by a 2-h interval. Following a 2-month recovery period, the cognitive status of the animals was assessed using the water maze task. ECS-treated animals were incapable of learning the constant platform position version of this task during the first 4 days of training, but performed similarly to control rats throughout the rest of the acquisition period, on the probe trial, and on the variable platform position and visible platform tasks. The results of the morphological analysis showed that the total number of hippocampal pyramidal neurons and dentate gyrus granule cells were similar in control and ECS-treated rats. However, ECS treatment caused loss of approximately 17% of cells in the hilus of the dentate gyrus, which was accompanied by significant mossy fiber sprouting into the dentate inner molecular layer. In addition, we found that the ECS-induced decrease in the total number of hilar cells was not due to loss of inhibitory interneurons immunoreactive to somatostatin. These findings support the view that ECS-induced seizures can produce a number of morphological and functional changes in the rat hippocampal formation, which qualitatively resemble those previously described in other seizure models.

Neurogenesis in the Dentate Gyrus of the Rat Following Electroconvulsive Shock Seizures

Electroconvulsive shock (ECS) seizures provide an animal model of electroconvulsive therapy (ECT) in humans. Recent evidence indicates that repeated ECS seizures can induce long-term structural and functional changes in the brain, similar to those found in other seizure models. We have examined the effects of ECS on neurogenesis in the dentate gyrus of the adult rat using bromodeoxyuridine (BrdU) immunohistochemistry, which identifies newly generated cells. Cells have also been labeled for neuronal nuclear protein (NeuN) to identify neurons. One month following eight ECS seizures, ECS-treated rats had approximately twice as many BrdU-positive cells as sham-treated controls. Eighty-eight percent of newly generated cells colabeled with NeuN in ECS-treated subjects, compared to 83% in sham-treated controls. These data suggest that there is a net increase in neurogenesis within the hippocampal dentate gyrus following ECS treatment. Similar increases have been reported following kindling and kainic acid- or pilocarpine-induced status epilepticus. Increased neurogenesis appears to be a general response to seizure activity and may play a role in the therapeutic effects of ECT.

Ketamine and phenobarbital do not reduce the evoked-potential enhancement induced by electroconvulsive shock seizures in the rat

Electroconvulsive shock (ECS) seizures provide an animal analog of electroconvulsive therapy (ECT). Repeated ECS seizures cause a long-lasting, and perhaps permanent, enhancement of entorhinal-dentate evoked potentials (EPs) in the rat. Recently it has been reported that ketamine protects against ECS-induced EP enhancement. The present study was designed to replicate these findings and to extend them by incorporating a phenobarbital group (to control for ketamine's partial diminution of seizures) and an animal test of antidepressant activity (the Porsolt test). Unexpectedly, we found that neither ketamine nor phenobarbital protected against ECS-induced enhancement of EPs. Both, however, diminished the ‘therapeutic’ effects of ECS, as modeled by the Porsolt test. These data suggest that the use of ketamine would not eliminate the unwanted effects of ECT and that it might diminish ECT's therapeutic benefits.

Mossy fiber sprouting induced by repeated electroconvulsive shock seizures

The elicitation of repeated focal seizures (kindling) induces mossy fiber sprouting in the hippocampus of the rat. The present study investigated whether repeated generalized seizures also induce mossy fiber sprouting. Human psychiatric patients receive repeated generalized seizures during electroconvulsive therapy (ECT). Male Long–Evans rats received a course of eight electroconvulsive shock (ECS) seizures administered on a 48-h schedule over a course of 2 1/2 weeks. Control subjects received matched handling, but no stimulation. Fourteen days after the last ECS trial, all subjects were sacrificed and their brains subjected to Timm staining. Cell counts and area measures were also taken in the hilus. Significant sprouting, but not significant cell loss, was seen in the fascia dentata of the subjects that had received ECS.

Long-term changes in entorhinal-dentate evoked potentials induced by electroconvulsive shock seizures in rats

Entorhinal-dentate evoked potentials were measured in rats before and after: (1) eight electroconvulsive shock (ECS) seizures, or (2) matched handling. In animals that received ECS, evoked potentials were significantly enhanced, as evidenced by a long-lasting increase in the amplitude of the population spike. This increase in population-spike amplitude lasted for at least 3 months after the last ECS trial. No evoked-potential changes were observed in the subjects that received matched handling. These data suggest that ECS seizures produce long-lasting, perhaps permanent, changes in the brain.

Increase of Methylguanidine and Guanidinoacetic Acid in the Brain of Amygdala‐Kindled Rats

Guanidino compounds are intrinsic chemoconvulsants. We investigated the regional and time-dependent changes of these compounds in the amygdala (AM) of kindled rats versus electroconvulsive shock (ECS) seizures using high-performance liquid chromatography (HPLC). Twenty-eight days after the last AM-kindled seizure, guanidinoacetic acid (GAA) and methylguanidine (MG) levels were significantly increased in the bilateral AM as compared with those of control rats, which had been implanted with electrodes but were not stimulated. Both compounds, however, tended to decrease in the bilateral AM after ECS seizure. In addition, we measured these compounds after induction of one afterdischarge (AD) in the AM. These compounds increased significantly 7 days after AD was induced in the ipsilateral AM. We suggest that the increase of these compounds is coincident with AD generation and specific to AM kindling and the kindled state.

Evidence for the interaction of brainstem systems mediating seizure expression in kindling and electroconvulsive shock seizure models

Amygdala kindling was observed to increase significantly the proportion of rats that exhibited tonic hindlimb extension in response to corneal electroshock stimulation. Mechanical brainstem lesions which abolished electroshock-induced tonic hindlimb extension failed to alter either the expression of fully generalized kindled seizures or the development of amygdala kindled seizures. Results suggest that while kindling can alter the sensitivity of brainstem systems involved in the expression of tonic hindlimb extension, these same systems are not necessary for either the development or expression of amygdala kindled seizures.

Evidence of hypothyroidism in the genetically epilepsy-prone rat

A number of neurochemical and behavioral similarities exist between the genetically epilepsy-prone (GEPR) rat and rats made hypothyroid at birth. These similarities include lower brain monoamine levels, audiogenic seizure susceptibility and lowered electroconvulsive shock seizure threshold. Given these similarities, thyroid hormone status was examined in GEPR rats. Serum samples were collected from GEPR-9 and non-epileptic control rats at 5, 9,13,16, 22, 31, 45, 60, 90, 150 and 350 days of age. Serum thyroxine (T 4) levels were significantly lower in GEPR-9 rats compared to control until day 22 of age. GEPR-9 thyrotropin (TSH) levels were significantly elevated during the period of diminished serum T 4. GEPR-9 triiodothyronine (T 3) levels were lower than control throughout the first year of life. The data indicate that the GEPR-9 rat is hypothyroid from at least the second week of life up to 1 year of age. The critical impact of neonatal hypothyroidism on brain function coupled with the development of the audiogenic seizure susceptible trait by the GEPR-9 rat during the third week after birth suggests that neonatal hypothyroidism could be one etiological factor in the development of the seizure-prone state of GEPR-9 rats.

Escape response thresholds in rats following repeated electroconvulsive shock seizures

Young male Fischer rats were given electroconvulsive seizures daily for seven days. Compared with sham controls, the treated rats were more responsive in an escape response threshold test to low-intensity near-threshold footshock 24 hr and 8 days later, when the last measurements were taken. An increase in intertrial responses was also noted for a few treated rats 24 hr, but not 8 days, after the last treatment. The effects appeared to be proactive, were not seen after a single seizure, and were independent of the intensity (50–150 mA) of shock used to induce the grand mal seizures.