Effects of physiological alterations and pharmacological agents on maximal electroshock seizure pattern and recovery time
Creators: name: Tedeschi, David Henry
Publisher: name: University of Utah
Year: 2012
Subjects: Electrophysiology - Experiments
Anticonvulsants

description: This study represents a systematic laboratory investigation of the effects of various physiological alterations and pharmacological agents on maximal electroshock seizure pattern and recovery time from such seizures, in an effort to elucidate further the mechanisms of seizures and the factors which influence them and the recovery process.  Maximal electroshock seizures (MES) were elicited in mice and rats by means of a Hans-Tech electroshock apparatus (60-cycle alternating current, 0.2-second stimulus duration, corneal electrodes) and the following variables of the seizure determined:  mean seizure duration, of tonic-hindleg flexion, tonic-hindleg extension, and a terminal generalized clonus, and the time required for 50 per cent of animals to recover the ability to exhibit a second after a first tonic-clonic seizure (RT50).  In rats, for age 29 days through 77 days, the severity of seizures tends to decrease (as measured by an increase in ratio, mean duration of tonic-hindleg flexion/mean duration of tonic-hindleg extension, F/E ratio), whereas RT50 tends to increase,  From age 83 days through 118 days, both the severity of seizures and TR50 are reasonably constant.  In mice, seizure severity and RT50 are reasonably constant.  In mice, seizure severity and RT50 tend to decrease and increase, respectively, between ages 30 days and 37 days; thereafter, both seizure severity and RT50 are reasonable constant through 114 days of age.  The data suggest that seizure severity and RT50 in both rats and mice tend to decrease and increase, respectively, with age, and that factors related to body growth appear to be responsible for these changes.  The duration of the tonic-hindleg flexor component of MES elicited in normal rats appears to be inversely related to the duration of the tonic-hindleg extensor component and directly related to RT50. Thus, in the absence of physical alterations or pharmacological agents, the inherently greater brain activity of animals with flexor components of short duration is reflected by a significantly decreased RT50; conversely, the inherently decreased brain activity of animals with flexor components of long duration is reflected by a significantly increased RT50.  Tonic-clonic seizures elicited in mice with higher stimulus intensities are more severe than those elicited by the standard 50 mA current.  In addition, RT50 increases with increased stimulus intensity.  The data obtained suggest that the physiological alterations which result from initial intense central nervous system stimulation and associated increased initial seizure severity delay recovery processes and/or raise the threshold for a second tonic-clonic seizure; the net effect in an increased RT50.  The severity of seizures elicited in chronically undernourished rats progressively increases throughout the period of undernourishment (28 days), In contrast, RT50 measured in undernourished rats' first increases and then gradually returns to normal.  It appears that the initial increase in RT50 is "stress" induced and that the gradual decrease of RT50 reflects the effects of increased adrenocortical activity.  Acute hyponatremia increases both seizure severity and RT50 in mice but does not significantly alter these variables in rats.  The fact that both seizure and Rt50 are increased in hyponatremic mice suggest that physiological alterations associated with acute hyponatremia tend directly to delay recovery processes.  Anticonvulsants drugs decrease seizure severity and increase RT50 in both mice and rats.  There does not appear to be a close relation between the effectiveness of these agents in altering MES pattern/or RT50 and their therapeutic usefulness, chemical structure, or anticonvulsant potency.  The increase of RT50 which results after anticonvulsant drug administration, for the most part, is attributable to a direct action of these compounds on recovery processes.  The order of recovery of second seizure components and seizure duration to their first seizure values in mice is as follows:  total seizure duration, clonus, tonic-hindleg extension, and lastly tonic-hindleg flexion.  This sequence of recovery indicates that the physiologic processes underlying tonic-hindleg flexion are most sensitive and those underlying clonus least sensitive to alteration in seizure severity; administration of diphenylhydatioin does not alter this relation.  The time required for 50 per cent of animal to recover the ability to exhibit a second after a first tonic-clonic seizure (RT50) is not significantly different from the time required for the F/E ration to reach a value which is reasonably constant for any one population sample.  Furthermore, the F/E/ ration at the time of the RT50 is not altered by anticonvulsant drug administration.  Both Phenobarbital and barbital induce qualitatively the same effects of MES pattern and ER50 in mice and rats: however, the difference in the magnitude of the effects of this drugs on tonic-hindleg flexion duration and RT50 indicates that Phenobarbital has certain anticonvulsant properties not shared to the same degree by barbital.  Strychnine markedly increases the severity of seizures and decrease RT50 in mice and rats.  These effects are accounted for by the well-known neuropharmacologic actions of this drug.  Picrotoxin increases the duration of tonic-hindleg flexion and tonic-hindleg extension in mice (no significant change in seizure severity as measured by the F/E ratio) and increases RT50 in this species.  The effects on RT50 are attributed to a prolonged period of postictal respiratory depression which occurs following drug-sensitization of the respiratory center.