title: Dialysis delivery of an adenosine A1 receptor agonist to the pontine reticular formation decreases acetylcholine release and increases anesthesia recovery time.
abstract: BACKGROUND
  Adenosine modulates cell excitability, acetylcholine release, nociception, and sleep. Pontine cholinergic neurotransmission contributes to the generation and maintenance of electroencephalographic and behavioral arousal. Adenosine A(1) receptors inhibit arousal-promoting, pontine cholinergic neurons, and adenosine enhances sleep. No previous studies have determined whether pontine adenosine also modulates recovery from anesthesia. Therefore, the current study tested the hypotheses that dialysis delivery of the adenosine A(1) receptor agonist N6-p-sulfophenyladenosine (SPA) into the pontine reticular formation would decrease acetylcholine release and increase the time needed for recovery from halothane anesthesia.
  
  
  METHODS
  A microdialysis probe was positioned in the pontine reticular formation of halothane-anesthetized cats. Probes were perfused with Ringer's solution (control) followed by the adenosine A(1) receptor agonist SPA (0.088 or 8.8 mm). Dependent measures included acetylcholine release and a numeric assessment of recovery from anesthesia. An intensive, within-subjects design and analysis of variance evaluated SPA's main effect on acetylcholine release and anesthetic recovery. The adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 microm) was coadministered with SPA to test for antagonist blocking of SPA's effects.
  
  
  RESULTS
  SPA significantly (P < 0.0001) decreased acetylcholine release in the pontine reticular formation and significantly (P < 0.0001) delayed recovery from anesthesia. Coadministration of SPA and DPCPX caused no decrease in acetylcholine release or delay in postanesthetic recovery. Dialysis delivery of SPA into the cerebellar cortex confirmed that the SPA effects were site-specific to the pontine reticular formation.
  
  
  CONCLUSIONS
  The results provide a novel extension of the sleep-promoting effects of adenosine by showing that pontine delivery of an adenosine A(1) receptor agonist delays resumption of wakefulness following halothane anesthesia. This extension is consistent with a potentially larger relevance of the current findings for efforts to specify neurons and molecules causing physiologic and behavioral traits comprising anesthetic states. These data support the conclusion that adenosine A(1) receptors in medial regions of the pontine reticular formation, known to modulate sleep, also contribute to the generation and/or maintenance of halothane anesthesia.
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-0615, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Tanase
authors.forename: Helen A
authors.initials: HA
authors.lastname: Baghdoyan
authors.forename: Ralph
authors.initials: R
authors.lastname: Lydic
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000161:Acoustic Stimulation; D000762:Anesthesia Recovery Period; D000818:Animals; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D004585:Electrooculography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011149:Pons / Q000187:drug effects*; D058906:Purinergic P1 Receptor Agonists; D012039:Regional Blood Flow / Q000187:drug effects; D012154:Reticular Formation / Q000187:drug effects*; D012867:Skin / Q000098:blood supply; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058906:Purinergic P1 Receptor Agonists; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000109:Acetylcholine; D010100:Oxygen