Articles

[The action profile of D,L-kavain. Cerebral sites and sleep-wakefulness-rhythm in animals]

Author

Holm E, Staedt U, Heep J, Kortsik C, Behne F, Kaske A, Mennicke I.

Date

7/1991

Journal

Arzneimittelforschung

Abstract

To investigate neurophysiological effects of D,L-kavain, two studies were conducted on unrestrained cats with chronically implanted electrodes. In group A animals (n = 26) we recorded the blood pressure, the EEG of cortical and subcortical areas, the electromyogram, EEG arousal reactions, and subcortical evoked potentials elicited by central stimulation. This was done before and after injection of D,L-kavain (10-50 mg/kg i.p.) or--for comparison--of a kava extract in Ol. arachidis (50-100 mg pyrones/kg i.p.). Group B cats (n = 9) served for polygraphic, 10-h analyses of the sleep-wakefulness rhythm; they received--in a random sequence--0.9% NaCl (3 ml i.p.), D,L-kavain (28 mg/kg p.o.), pentobarbital (1 mg/kg i.m.), or the combination D,L-kavain plus pentobarbital. With both D,L-kavain and the extract, muscle tone was seen to be diminished in about 50% of the experiments. It was only the extract which exerted marked effects on the EEG; it induced high amplitude delta waves, spindle-like formations, and a continuous alpha- or beta-synchronization in the amygdalar recordings (p less than 0.001). Neither D,L-kavain nor the kava extract changed the threshold of the EEG arousal reaction. As to the evoked potentials, the hippocampal response following stimulation of the amygdalar nucleus showed an increase in amplitude in the animals given D,L-kavain (50 mg/kg; p less than 0.05) and in those given the extract (100 mg pyrones/kg; p less than 0.01). In addition, after injection of the extract, further projections arising from the amygdala as well as the connection from the caudate nucleus to the amygdala proved to be activated. The percentage duration of active wakefulness was significantly shortened by both D,L-kavain and pentobarbital, as compared to placebo. There was a likewise significant prolongation of synchronized sleep with D,L-kavain, pentobarbital, and the combination of both these agents. However, a potentiation of drug effects failed to occur. It is concluded from the findings that limbic structures and, in particular, the amygdalar complex represent the preferential site of action for both D,L-kavain and the kava extract. The participation of these structures in modulating emotional processes may explain the promotion of sleep, even in the absence of sedation. There is no congruity of D,L-kavain with either the tricyclic thymoleptics or the benzodiazepines regarding the profile of neurophysiological effects.