Role of adenosine in behavioral state modulation: A microdialysis study in the freely moving cat

C. M. Portas, M. Thakkar, D. G. Rainnie, R. W. Greene, R. W. McCarley

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

There is considerable evidence to suggest that the activity of forebrain and mesopontine cholinergic neurons is intimately involved in electroencephalographic arousal. Furthermore, our previous in vitro investigation suggested that both cholinergic systems are under a powerful tonic inhibitory control by endogenous adenosine. We thus examined in the in vivo effect, on electrographically defined behavioral states, of microdialysis perfusion of adenosine into the cholinergic zones of the substantia innominata of the basal forebrain and the laterodorsal tegmental nucleus of freely moving cats. Localized perfusion of adenosine into either the basal forebrain or the laterodorsal tegmental nucleus caused a marked alteration in sleep wake architecture. Adenosine (300 μM) perfused into either the basal forebrain or laterodorsal tegmental nucleus produced a dramatic decrease in waking, to about 50% of the basal level. Perfusion into the basal forebrain resulted in a significant increase in rapid eye movement sleep, while slow wave sleep was unchanged. In contrast, adenosine perfusion into the laterodorsal tegmental nucleus produced an increase of both slow wave sleep and rapid eye movement sleep, the magnitude of which were proportional to the decrease in waking. Electroencephalographic power spectral analysis showed that adenosine perfusion into the basal forebrain increased the relative power in the data frequency band, whereas higher frequency bands (theta, alpha, beta and gamma) showed a decrease. These data strongly support the hypothesis that adenosine might play a key role as an endogenous modulator of wakefulness and sleep. The decrease in wakefulness may 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 present, is uncertain. The observation that local perfusion of adenosine into either the basal forebrain on the laterodorsal tegmental nucleus dramatically decreases wakefulness suggests that these areas might represent a major site of action of the xanthine stimulants (adenosine antagonists) found in coffee and tea.

Original languageEnglish (US)
Pages (from-to)225-235
Number of pages11
JournalNeuroscience
Volume79
Issue number1
DOIs
StatePublished - Apr 28 1997

Fingerprint

Microdialysis
Adenosine
Cats
Sleep
Perfusion
Wakefulness
REM Sleep
Cholinergic Neurons
Cholinergic Agents
Substantia Innominata
Xanthine
Coffee
Tea
Prosencephalon
Basal Forebrain
Arousal

Keywords

  • Adenosine
  • Basal forebrain
  • Behavioral states
  • Laterodorsal tegmentum
  • Microdialysis
  • REM sleep

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of adenosine in behavioral state modulation : A microdialysis study in the freely moving cat. / Portas, C. M.; Thakkar, M.; Rainnie, D. G.; Greene, R. W.; McCarley, R. W.

In: Neuroscience, Vol. 79, No. 1, 28.04.1997, p. 225-235.

Research output: Contribution to journalArticle

Portas, C. M. ; Thakkar, M. ; Rainnie, D. G. ; Greene, R. W. ; McCarley, R. W. / Role of adenosine in behavioral state modulation : A microdialysis study in the freely moving cat. In: Neuroscience. 1997 ; Vol. 79, No. 1. pp. 225-235.
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