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Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep. 2006

Christal G Coleman, and Helen A Baghdoyan, and Ralph Lydic
Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-0615, USA.

In vivo microdialysis in C57BL/6J (B6) mouse was used to test the hypothesis that activating adenosine A(2A) receptors in the pontine reticular formation (PRF) increases acetylcholine (ACh) release and rapid eye movement (REM) sleep. Eight concentrations of the adenosine A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; CGS) were delivered to the PRF and ACh in the PRF was quantified. ACh release was significantly increased by dialysis with 3 mum CGS and significantly decreased by dialysis with 10 and 100 microm CGS. Co-administration of the adenosine A(2A) receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385; 30 nM) blocked the CGS-induced increase in ACh release. In a second series of experiments, CGS (3 microm) was delivered by dialysis to the PRF for 2 h while recording sleep and wakefulness. CGS significantly decreased time in wakefulness (-51% in h 1; -54% in h 2), increased time in non-rapid eye movement (NREM) sleep (90% in h 1; 151% in h 2), and increased both time in REM sleep (331% in h 2) and the number of REM sleep episodes (488% in h 2). The enhancement of REM sleep is consistent with the interpretation that adenosine A(2A) receptors in the PRF of the B6 mouse contribute to REM sleep regulation, in part, by increasing ACh release in the PRF. A(2A) receptor activation may promote NREM sleep via GABAergic inhibition of arousal promoting neurons in the PRF.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009433 Neural Inhibition The function of opposing or restraining the excitation of neurons or their target excitable cells. Inhibition, Neural
D009434 Neural Pathways Neural tracts connecting one part of the nervous system with another. Neural Interconnections,Interconnection, Neural,Interconnections, Neural,Neural Interconnection,Neural Pathway,Pathway, Neural,Pathways, Neural
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D010627 Phenethylamines A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed) Phenylethylamines
D011149 Pons The front part of the hindbrain (RHOMBENCEPHALON) that lies between the MEDULLA and the midbrain (MESENCEPHALON) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the CEREBELLUM to the CEREBRUM. Pons Varolii,Ponte,Pons Varolius,Pontes,Varolii, Pons,Varolius, Pons
D012154 Reticular Formation A region extending from the PONS & MEDULLA OBLONGATA through the MESENCEPHALON, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. Formation, Reticular,Formations, Reticular,Reticular Formations
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt

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