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Withdrawal-produced increase in susceptibility to kindled seizures following a single injection of alcohol in rats

University of British Columbia

It has been well-established in both humans and laboratory animals that the withdrawal of alcohol after a period of chronic exposure can have convulsive effects. In the present studies, however, such convulsive effects were detected in naive rats following the metabolism of a single ethanol injection. These effects were assessed by measuring the duration of kindled motor seizures (MSs) and electrographic after discharges (ADs) elicited by low-intensity amygdaloid stimulation at intervals before, during, and after the exposure. Kindled MSs are those which can be reliably elicited only after an organism has been stimulated periodically with an initially ineffective low-intensity current. Thus, before each experiment the subjects were kindled with the periodic amygdaloid stimulation until MSs and ADs of stereotypical duration and pattern were reliably elicited. The consistency of the kindled seizures provided a stable baseline against which to assess the convulsive effects of the withdrawal of ethanol. In Experiment 1 kindled seizures were elicited at fixed intervals before and after a single intraperitoneal injection of ethanol. Changes in the AD and MS duration revealed a potent anticonvulsive effect in the 3 hr immediately following the injection, followed about 12 hr later by a convulsive effect lasting about 5 hr. In Experiment 2 this effect was replicated and directly related to changes in the level of blood ethanol. The anticonvulsive effect was related to the presence of the ethanol while the convulsive effects seemed to be triggered by its metabolism. In Experiments 3 and 4 a different experimental design was used to study the effects of single intraperitoneal and intragastric injections, respectively. Since in these experiments only one seizure was elicited in each subject after the alcohol injection, the possibility that the increase in seizure duration was an artifact of the repeated testing procedure rather than a bona fide withdrawal-produced effect was ruled out. Thus, the results confirmed previous demonstrations of convulsive effects following the metabolism of single injections of ethanol. This established the generality of the phenomenon to other species, modes of ethanol administration, and to different experimental designs; and the utility of the kindling paradigm for studying the time course of anticonvulsive and convulsive effects. The changes underlying the manifestation of severe convulsive effects obvious in humans after withdrawal from chronic ethanol exposure appears to develop with an individual's first exposure.

Text

2010-01-29

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http://hdl.handle.net/2429/19428

Psychology

University of British Columbia

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