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H Lesse

Publications and source records attributed to H Lesse.

8 recordsLinked to original sources
PubMed1985

Frequency-related, bidirectional limbic responses to cocaine: comparisons with amphetamine and lidocaine.

Dual effects of cocaine on the electrical excitability of limbic structures were investigated by determining current thresholds for afterdischarges (AD) evoked by low and high frequency electrical stimulation. Cocaine, lidocaine and D-amphetamine treatments were compared in order to assess the extent to which cocaine's local anesthetic and monoaminergic actions contribute to its effects on limbic afterdischarges. Afterdischarge threshold, duration and propagation for both 3 and 50 Hz stimulation of the amygdala, hippocampus and septal area were tested following saline, cocaine (5 mg/kg), lidocaine (5 mg/kg) and D-amphetamine (2.5-5 mg/kg). Results provide clear evidence that cocaine has a bidirectional effect on hippocampal and amygdalar AD thresholds--significantly increasing sensitivity to low frequency stimulation while significantly decreasing sensitivity to high frequency stimulation at identical brain sites. A frequency-dependent threshold effect also occurred at the septal area. In addition, cocaine reduced limbic AD duration and propagation; these effects proved unrelated to the direction of AD threshold changes. Cocaine effects on afterdischarges differed significantly from those of amphetamine and lidocaine. Comparisons with amphetamine and lidocaine suggest that cocaine's local anesthetic action, but not its monoaminergic properties, may contribute to reductions in limbic afterdischarge duration and propagation. However, it is unlikely that either monoaminergic or local anesthetic actions are responsible for cocaine's pronounced dual effect on the electrical excitability of major limbic structures. This bidirectional drug effect has interesting neurobiological implications and, in addition, offers a potentially valuable tool for new research on frequency-related functions of the limbic system.

Amygdala↗
PubMed1984

Regional effects of ethanol on limbic afterdischarge activity.

This study assessed the effects of acute administration of ethanol on afterdischarge (AD) activity evoked by electrical stimulation of the amygdala, septum and hippocampus. Limbic AD thresholds, duration and propagation were determined in cats following intravenous infusions of saline or ethanol (0.4, 0.8 and 1.6 g/kg). Ethanol administrations significantly increased septal and amygdalar, but not hippocampal AD thresholds. This effect was dose-related and most pronounced at the septum. Reductions in AD duration followed ethanol treatment and demonstrated similar regional differences. In addition, projected discharges were reduced, propagation of AD from stimulation sites to limbic and neocortical projections sites were suppressed and ictal episodes were attenuated following ethanol treatment. Afterdischarge activity was affected even by the 0.4 g/kg dose which produced no observable change in behavior. These findings indicate that ethanol reduces the responsiveness of limbic structures to electrical stimulation--suppressing the initiation, maintenance and propagation of limbic afterdischarges. The amygdala, septum and hippocampus proved differentially sensitive to ethanol.

Action Potentials↗
PubMed1980

Differential effects of cocaine on limbic excitability.

Effects of cocaine on the initiation and maintenance of electrically induced limbic afterdischarges (AD) were studied in cats. Current thresholds for evoking AD in the hippocampus, amygdala and septal region were determined following alternating saline and cocaine administrations. Three subconvulsant doses (1--10 mg/kg, IM) were tested at 96 hour intervals. The cocaine administrations significantly decreased the current required to initiate AD in both the hippocampus and amygdala. This effect was dose-related; it was found when limbic discharges were localized and also after fully developed motor convulsions were evoked. By contrast, septal AD thresholds were unchanged. In addition, dose-related reductions in AD duration were induced at all limbic sites tested. Restrictions in propagation to distant sites occurred during early stages of seizure development. Progressive changes did not develop following either repeated tests of single-dose effects or during a six week period of daily cocaine administration. These results suggest that cocaine has preferential excitatory effects on closely related limbic structures, increasing the sensitivity of the hippocampus and amygdala to direct electrical stimulation. A concurrent, independent inhibitory action is implied by the reduced duration of limbic afterdischarges. The absence of progressive electrophysiological responses suggests that there is no potentiation of limbic excitatory effects following the repeated administration of doses which do not induce focal epileptiform activity.

Animals↗
PubMed1979

Behavioral antecedents of cocaine-induced stereotypy.

The effect of cocaine on discriminative behavior was determined in a study in which the subjects' ongoing behavior at the time of drug administration was manipulated. Cats were trained in a discrimination task where bar-pressing when a tone was present (S+) resulted in milk reinforcement. When the tone was absent (S-) milk was not delivered. The duration of these periods varied randomly during 30-min sessions and responses during S- delayed the next trial. Once a high level of discrimination was achieved, drug testing was begun. Ongoing behavior was manipulated by scheduling either a 5-min S+ or S- period immediately after cocaine injection (1 mg/kg). When S+ followed cocaine, stereotyped bar-pressing developed with markedly increased responding during the remainder of the session. In contrast, when S- followed cocaine, suppression of bar-pressing developed. The effect could be reversed in most subjects when stimulus conditions were later reversed. A similar experiment using rats yielded similar results. These results indicate that ongoing behavior and stimulus conditions are critically important in determining the behavioral effects of cocaine.

Animals↗
PubMed1979

Effects of cocaine on propagation of limbic seizure activity.

Effects of cocaine on the spread of epileptiform discharges within the limbic system were studied in cats prepared with bilateral arrays of indwelling electrodes. Low frequency focal electrical stimulation at threshold intensity was employed to initiate after-discharges in the hippocampus and amygdala. Latencies for the propagation of epileptiform activity to distant limbic sites were determined. Saline and drug tests were alternated, with 96-hr intervals between cocaine administrations. Three subconvulsant doses (1--10 mg/kg cocaine hydrochloride, injected intramuscularly) were tested in a counterbalanced order. Cocaine administration significantly increased the speed at which epileptiform discharges spread to the amygdala and to the hippocampus. This effect was dose-related, it followed both hippocampal and amygdalar stimulation and was evident in ipsilateral as well as contralateral projection sites. These changes were found when limbic seizure patterns were localized and also after fully developed motor convulsions were evoked. In addition, cocaine decreased the duration of the propagated discharges. These results suggest that subconvulsive doses of cocaine have an excitatory effect on the hippocampus and amygdala, increasing their sensitivity to repetitive discharges originating in distant sites. A concurrent inhibitory effect is suggested by the decreased duration of the propagated discharges.

Amygdala↗