Enhancement of rapid eye movement sleep in the rat by actions at A1 and A2a adenosine receptor subtypes with a differential sensitivity to atropine.
The adenosine agonist cyclohexaladenosine injected into the medial pontine reticular formation of the rat induces a long-lasting increase in rapid eye movement sleep. To investigate the adenosine receptor-subtype(s) mediating this effect, the dose-response relationships for increasing rapid eye movement sleep by two highly selective adenosine receptor agonists were compared. Rats were surgically prepared for chronic sleep recording and bilateral guide cannulae were aimed at medial sites in the caudal, oral pontine reticular formation. Injections were made unilaterally in 60 nl volumes within 1 h after lights-on. The adenosine agonists used were A1-selective cyclohexaladenosine (10(-6)-10(-4) M) and A2a-selective CGS 21680 (10(-7)-10(-3) M). Each animal also received a series of three, paired-consecutive injections of the muscarinic receptor antagonist atropine (4x10(-3) M) followed by the lowest effective dose of each agonist or saline as control. The A2a receptor agonist, CGS 21680, was one order of magnitude more potent than the A1 receptor agonist, cyclohexaladenosine, in inducing rapid eye movement sleep increases. Preinjection of atropine at a dose that did not itself affect rapid eye movement sleep resulted in antagonism of CGS 21680, but not cyclohexaladenosine-induced rapid eye movement sleep. The differential sensitivity of these ligands to antagonism by atropine supports the conclusion that both A1 and A2a adenosine receptor subtypes in the reticular formation subserve agonist-induced rapid eye movement sleep and that they do so by independent mechanisms. The A2a mechanism requires the cholinergic system and may act through the increased release of acetylcholine. The A1 mechanism operates at a different locus possibly through an inhibition of GABA neurotransmission.
Marks
G A
GA
The University of Texas Southwestern Medical Center at Dallas, 75235-9070, USA. gmarks@mednet.swmed.edu
Shaffery
J P
JP
Speciale
S G
SG
Birabil
C G
CG
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D020318:Rats, Long-Evans; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology
D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D001285:Atropine