R. F. Mucha

Postseizure inhibition of kindled seizures

Abstract Rats were kindled until each periodic, bipolar, amygdaloid stimulation reliably elicited and afterdischarge and a generalized motor seizure. The inhibitory effects of one amygdaloid stimulation (antecedent stimulation) on the afterdischarges and motor seizures typically produced by the next (test stimulation) were studied in a series of experiments. Levels of antecedent stimulation which themselves elicited afterdischarges and motor seizures produced marked inhibitory effects which dissipated in approximately 90 min, whereas levels of antecedent stimulation which elicited local afterdischarges but no motor seizures had only mild inhibitory consequences. Regardless of their intensity, stimulations which evoked no epileptic responses themselves did not inhibit the responses to subsequent test stimulations. The inhibitory effect of a series of antecedent stimulations was more complex than that produced by a single stimulation. A series of 19 kindled motor seizures was elicited by amygdaloid stimulations applied at 1.5-h intervals without any indication of inhibitory effects; however, the next day the response to a single amygdaloid stimulation was almost completely suppressed. This marked inhibitory effect dissipated gradually during the next 5 days.

Kindling‐Related Changes in Afterdischarge “Thresholds”

Amygdaloid stimulations were applied to rats at gradually increasing current intensities once every 60 sec until an afterdischarge (AD) was recorded through the stimulation electrode. These initial AD “thresholds” (x = 75 μA) were reduced over a 4‐day period by a series of 12 subthreshold stimulations. In contrast, stimulations administered on the same regimen but at a higher intensity (400 μA) had raised the AD threshold. The decreases in the AD threshold were relatively permanent, whereas the elevated thresholds were subsequently reduced to control levels by a series of subthreshold stimulations or by a 7‐day stimulation‐free period. Two days following the completion of Experiment 1, all of the rats were injected with a low dose of pentylenetetrazol. The incidence of pentylenetetrazol‐induced epileptic symptoms was much higher in the experimental animals than in the control subjects previously subjected only to the threshold estimation procedure.

Spontaneous seizures generated in rats by kindling: A preliminary report

Daily amygdaloid stimulation administered to rats at current levels initially too low to produce a motor response but high enough to produce an electrographic afterdischarge (AD) resulted in the progressive development and intensification of stimulus-induced epileptic activity (kindling). In contrsst to previous studies, however, stimulation was continued long after the point where the exacerbation of motor seizures (MSs) seemed complete. Several animals were stimulated for up to 7 months and, with continued stimulation, an epileptic syndrome characterized by spontaneous motor seizures was observed to develop.

Intensification of the alcohol withdrawal syndrome by repeated brain stimulation.

SINCE the discovery that electrical stimulation of discrete sites of the brain can influence behaviour, there have been numerous reports of its application1. Such procedures, however, may lead to kindling2; stimulation of some sites at currents initially too low to produce a behavioural response may lead to a gradual development and then intensification of seizures evoked by the stimulation3. Thus when the brain is repeatedly stimulated for therapeutic purposes, seizures may be elicited unless procedures not conducive to kindling are used2. Two questions arise: can kindling leave an organism more susceptible to seizures produced by agents other than local brain stimulation, and are elicited convulsions necessary for this change in susceptibility? Our findings indicate that whether or not overt convulsions are produced by brain stimulation, repeated electrical stimulation of the brain potentiates the effects of subsequent alcohol withdrawal.

Temporary effects of periodic alcohol availability

Both experimental and control rats received continuous access to laboratory chow, water, and a 20% ethanol solution for the 105 days of the experiment except that the access of the experimental animals to the ethanol solution was limited to alternate days between days 35 and 93. Under conditions of periodic alcohol availability, there was a progressive increase in the relative selection of ethanol solutions on days when both ethanol and water were available; however, the high levels of alcohol selection induced by the periodic availability were not maintained when the experimental animals were again offered continuous access to the alcohol solutions.

Simple method for producing an alcohol withdrawal syndrome in rats

Rats received intragastric intubations of ethanol at 8 hr intervals for 1, 7, 15 or 30 days. The dosage for each animal was one which produced observable signs of intoxication 1 hr after the intubation. All of the rats in the experimental groups developed a tolerance to ethanol as indicated by the increasing dose required to induce intoxication, but the degree of tolerance was related to the duration of the ethanol administration. During the withdrawal period the incidence of hyperreactivity, convulsive symptoms, and the susceptibility to audiogenic seizures was determined for all 4 groups. Although every experimental animal displayed withdrawal symptoms, the incidence of these symptoms was found to be an increasing, negatively accelerated function of the duration of ethanol exposure. For situations where voluntary consumption of alcohol is not necessary this method is a simple, controlled, reliable, way of inducing ethanol tolerance and physical dependence in rats.

Suppression of voluntary ethanol consumption in rats by electroconvulsive shock

When ethanol solutions were presented on alternate days to rats with continuous access to food and water, there was a progressive increase in alcohol selection. However, this increase could be blocked or eliminated, once established, by a series of daily electroconvulsive shocks (ECSs). Two additional experiments suggested that this effect was not the result of a taste aversion conditioned to the noxious aftereffects of the ECS. In Experiment 2 the increase in alcohol selection produced by the periodic regimen was blocked by a series of ECSs which was completed 24 hr before the first presentation of ethanol; and in Experiment 3 a standard conditioned taste-aversion paradigm was employed with ECS in lieu of the usual emetic and there was no evidence of a conditioned taste aversion even after multiple trials. In a fourth experiment increases in the consumption of a sodium-saccharin solution presented on an alternate-day schedule were blocked by a series of ECSs. Thus, it appears that neither the effect of periodic availability on consumption nor its disruption by ECS are specific to ethanol solutions.

Role of footshock-produced activity and reactivity functions in the production of incubation and Kamin gradients.

Rats received ten noncontingent footshocks (FSs) in the start compartment of a two-compartment box followed 1 min, 1 hr, 4 hr, or 24 hr later by a test of one-way active avoidance. Two kinds of tests were employed, only one of which involved the administration of additional FSs. The animals receiving no FS during the test were placed in the start compartment and their active-avoidance latencies were measured; the other animals received FS during the course of ten one-way active avoidance trials. In the no-FS condition, avoidance deteriorated monotonically over 24 hr, but in the FS condition the usual U-shaped Kamin effect was observed. Independent activity measures prior to each avoidance trial suggested that both of these functions resulted from FS-produced, time-related changes in activity or reactivity. When no FS was administered during the test, activity decreased monotonically over the four FS-test intervals; whereas the reactivity to additional FSs administered during the test was a U-shaped function. These data clearly demonstrate the important role played by activity and reactivity functions in the production of the incubation and Kamin effects respectively.