Role of adenosine in behavioral state modulation: a microdialysis study in the freely moving cat
Section snippets
Experimental procedures
Adult cats (3–3.5 kg, n=12) were pre-anesthetized with a mixture of ketamine hydrochloride (100 mg/ml) and acepromazine maleate (10 mg/ml) at a dose of 0.1 ml/kg (i.p.). This treatment allowed an intravenous catheter to be inserted into the forelimb so that sodium pentobarbital (30 mg/kg, i.v.) could be fractionally administered to obtain and maintain deep surgical anesthesia. Cats were then stereotaxically implanted with electrodes to record EEG, electro-oculogram and electromyogram (EMG). In
Histology
In nine of the 10 cases described here as BF perfusion, the probe tip was found to be located within the SI. A typical photomicrograph of a coronal section of the cat BF (approximately A 15)[5]illustrating the area of perfusion in the SI is shown in Fig. 1a. In one animal the tip of the probe was localized to the cholinergic zone of the septum, including the DBB. For each of the six cases described as LDT perfusion, the probe tip was found to be located within the LDT, as shown in the
Discussion
These data provide evidence that adenosine, through local actions within the cholinergic nuclei of the LDT or the BF, strongly decreases waking. These data further support the hypothesis that adenosine acts as an endogenous modulator of behavioral state, as originally postulated by Radulovacki,[35]and more specifically, is consistent with the hypothesis that adenosine-mediated inhibition localized to the cholinergic arousal centers decreases waking, thus providing a link between cellular
Conclusion
We have demonstrated that local adenosine perfusion into the BF or LDT resulted in a significant decrease in waking. We suggest that this decrease most probably results from a direct inhibition of cholinergic neurons. However, as neither the LDT nor the BF is a homogeneous neuronal population, a greater understanding of the effects of adenosine on non-cholinergic neurons in these two regions is required to substantiate this hypothesis. Moreover, adenosine acts to reduce glutamate transmission
References (60)
- et al.
Restoration of brain energy metabolism as the function of sleep
Prog. Neurobiol.
(1995) - et al.
Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation
Brain Res.
(1995) - et al.
Afferent and efferent connections of the laterodorsal tegmental nucleus in the rat
Brain Res. Bull.
(1990) The physiological role of adenosine in the central nervous system
Int. Rev. Neurobiol.
(1985)- et al.
Modulation of neurotransmission by purine nucleotides and nucleosides
Biochem. Pharmac.
(1980) - et al.
The electrophysiology of adenosine in the mammalian central nervous system
Prog. Neurobiol.
(1991) - et al.
Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats
Neuroscience
(1996) The organization of central cholinergic systems and their functional importance in sleep–waking states
Prog. Brain Res.
(1993)- et al.
Afferents to the basal forebrain cholinergic cell area from pontomesencephalic-catecholamine, serotonin, and acetylcholine-neurons
Neuroscience
(1989) - et al.
Firing of “possibly” cholinergic neurons in the rat laterodorsal tegmental nucleus during sleep and wakefulness
Brain Res.
(1992)
A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats
Brain Res.
Brain stem modulation and REM sleep
Sem. Neurosci.
Microdialysis: a system for localized drug delivery into the brain
Brain Res. Bull.
Caffeine produces REM sleep rebound in rats
Brain Res.
Physiological evidence for subpopulations of cortically projecting basal forebrain neurons in the anesthetized rat
Neuroscience
Immunohistochemical detection of A1 adenosine receptors in rat brain with emphasis on localization in the hippocampal formation, cerebral cortex, cerebellum, and basal ganglia
Brain Res.
Effects of theophylline on nocturnal sleep and daytime sleepiness/alertness
Chest
Organization of central cholinergic systems
Prog. Brain Res.
Projections of cholinergic and non-cholinergic neurons of the brainstem core to relay and associational thalamic nuclei in the cat and macaque monkey
Neuroscience
Evidence for a projection from the lateral preoptic area and substantia innominata to the “mesencephalic locomotor region” in the rat
Brain Res.
Sleep-related neuronal discharge in the basal forebrain of cats
Brain Res.
Sleep–waking discharge of basal forebrain projection neurons in cats
Brain Res. Bull.
Effect of rapid eye movement sleep deprivation on 5′-nucleotidase in the brain
Neurosci. Lett.
Role of adenosine in sleep and temperature regulation in the preoptic area of rats
Pharmac. Biochem. Behav.
The effects of adenosine and 2′-deoxycoformycin on sleep and wakefulness in rats
Neuropharmacology
Cholinergic systems in the rat brain: III. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain
Brain Res. Bull.
The dose–response effects of caffeine on sleep in rats
Brain Res.
REM sleep deprivation up-regulates adenosine A1 receptors
Brain Res.
Purine levels in the intact rat brain. Studies with an implanted perfused hollow fibre
Neurosci. Lett.
Simultaneous pontine and basal forebrain microinjections of carbachol suppress REM sleep
J. Neurosci.
Cited by (184)
Astrocyte-neuron circuits in epilepsy
2023, Neurobiology of DiseaseTrihexyphenidyl increases delta activity in non-rapid eye movement sleep without impairing cognitive function in rodent models
2022, NeuropharmacologyCitation Excerpt :It suggested that BF cholinergic neurons might be suppressed during sleep rebound. It fits with the observation that, microinjection of adenosine, a neuromodulator to inhibit BF cholinergic neurons, produced a dramatic decrease in wakefulness by 50% (Portas et al., 1997). It is still lacking of evidence if BF cholinergic neurons are suppressed or activated in chronic sleep insufficiency condition.
Neural consequences of chronic sleep disruption
2022, Trends in NeurosciencesDesign, synthesis and biological evaluation of Tozadenant analogues as adenosine A<inf>2A</inf> receptor ligands
2021, European Journal of Medicinal ChemistryExploring the nap paradox: are mid-day sleep bouts a friend or foe?
2017, Sleep Medicine