ROLE OF ADENOSINE IN BEHAVIORAL STATE MODULATION - A MICRODIALYSIS STUDY IN THE FREELY MOVING CAT

There is considerable evidence to suggest that the activity of forebra in and mesopontine cholinergic neurons is intimately involved in elect roencephalographic arousal. Furthermore, our previous in vitro investi gation suggested that both cholinergic systems are under a powerful to nic inhibitory control by endogenous adenosine. We thus examined the i n vivo effect, on electrographically defined behavioral states, of mic rodialysis perfusion of adenosine into the cholinergic zones of the su bstantia innominata of the basal forebrain and the laterodorsal tegmen tal nucleus of freely moving cats. Localized perfusion of adenosine in to either the basal forebrain or the laterodorsal tegmental nucleus ca used a marked alteration in sleep-wake architecture. Adenosine (300 mu M) perfused into either the basal forebrain or laterodorsal tegmental nucleus produced a dramatic decrease in waking, to about 50% of the b asal level. Perfusion into the basal forebrain resulted in a significa nt increase in rapid eye movement sleep, while slow wave sleep was unc hanged. In contrast, adenosine perfusion into the laterodorsal tegment al nucleus produced an increase of both slow wave sleep and rapid eye movement sleep, the magnitude of which were proportional to the decrea se in waking. Electroencephalographic power spectral analysis showed t hat adenosine perfusion into the basal forebrain increased the relativ e power in the delta frequency band, whereas higher frequency bands (t heta, alpha, beta and gamma) showed a decrease. These data strongly su pport the hypothesis that adenosine might play a key role as an endoge nous modulator of wakefulness and sleep. The decrease in wakefulness m ay be directly related to the inhibition of cholinergic neurons of the basal forebrain and the laterodorsal tegmentum. The increase in rapid eye movement sleep is a novel but robust effect whose origin, at pres ent, is uncertain. The observation that local perfusion of adenosine i nto either the basal forebrain or the laterodorsal tegmental nucleus d ramatically decreases wakefulness suggests that these areas might repr esent a major site of action of the xanthine stimulants (adenosine ant agonists) found in coffer and tea.