Sleep, EEG and behavioral responses after systemic administration of gaboxadol in the laboratory cat

Abstract

GABA and its receptors are widely distributed in sleep-wakefulness cycle (SWC) network structures, but action of extrasynaptic GABAA receptors in SWC mechanisms is not yet fully understood. The cat has been extensively used in SWC research, but to our knowledge there are no previous studies about the response of this species to the administration of gaboxadol, an extrasynaptic GABAA receptor agonist. The present study aims to characterize the effects of systemic gaboxadol administration on SWC states, EEG and behavior in laboratory cats. Four adults cats with electrodes for chronic sleep polygraphic recordings were used. Gaboxadol (doses 0.2–10.0 mg/kg) and saline were i.p. administered. Polygraphic-video recordings were obtained for 8 h post-injections. The lowest doses of gaboxadol (0.2, 0.5 and 1 mg/kg) produced little effect on SWC state proportions and polygraphic patterns were associated with normal postural behavioral and autonomic behaviors. Power spectra analyses showed EEG features of NREM sleep to be in the range of delta band values for spontaneous slow wave sleep (SWS). Administration of the largest dose (10 mg/kg) produced continuous slow waves in the EEG associated with odd postures, stuporous behavior, shallow breathing and markedly increased respiratory rate. Intermediate doses (2 and 5 mg/kg), did not have these undesirable effects and the cats alternated between different SWC states, with an enhancement of slow wave EEG activity duration. However, during the first 4 h of the recordings, the periods that could be scored as SWS on the basis of this slow wave EEG activity, were dissociated from behavior, as the animals remained with eyes open in a postural attitude typical of relaxed wakefulness or drowsiness. During these episodes the cats barely closed their eyes only when PGO waves appeared in the lateral geniculate nucleus recordings. In spite of the EEG/behavioral uncoupling in these experiments, power spectra analyses indicated a definite increased delta band during EEG slow wave activity. REM sleep episodes presented all the typical electrophysiological and behavioral characteristics and the proportions of the REM sleep remained fairly stable. Gaboxadol in cats produce SWC responses similar to that described in other species including man, but there is an unusual EEG/behavioral dissociation under gaboxadol that could be exploited to investigate extrasynaptic GABAA receptors not only in SWS but also in wakefulness. Supported by Grant BFU2009-06991 from MCyT, Spain