title: Fentanyl and morphine, but not remifentanil, inhibit acetylcholine release in pontine regions modulating arousal.
abstract: BACKGROUND
  Opioids inhibit the rapid eye movement (REM) phase of sleep and decrease acetylcholine (ACh) release in medial pontine reticular formation (mPRF) regions contributing to REM sleep generation. It is not known whether opioids decrease ACh release by acting on cholinergic cell bodies or on cholinergic axon terminals. This study used in vivo microdialysis to test the hypothesis that opioids decrease ACh levels at cholinergic neurons in the laterodorsal tegmental nuclei (LDT) and LDT axon terminals in the mPRF.
  
  
  METHODS
  Nine male cats were anesthetized with halothane, and ACh levels within the mPRF or LDT were assayed using microdialysis and high-pressure liquid chromatography (HPLC). ACh levels were analyzed in response to dialysis of the mPRF and LDT with Ringer's solution (control), followed by dialysis with Ringer's solution containing morphine sulfate (MSO4) or naloxone. ACh in the mPRF also was measured during either dialysis delivery or intravenous infusion of remifentanil and during dialysis delivery of fentanyl.
  
  
  RESULTS
  Compared with dialysis of Ringer's solution, microdialysis with MSO4 decreased ACh by 23% in the mPRF and by 30% in the LDT. This significant decrease in ACh was antagonized by naloxone. MSO4 and fentanyl each caused a dose-dependent decrease in mPRF ACh when delivered by dialysis. Remifentanil delivered by continuous intravenous infusion or by dialysis into the mPRF did not alter mPRF ACh.
  
  
  CONCLUSIONS
  Morphine inhibits ACh at the cholinergic cell body region (LDT) and the terminal field in the mPRF. ACh in the mPRF was not altered by remifentanil and was significantly decreased by fentanyl. Thus, MSO4 and fentanyl disrupt cholinergic neurotransmission in the LDT-mPRF network known to modulate REM sleep and cortical electroencephalographic activation. These data are consistent with the possibility that inhibition of pontine cholinergic neurotransmission contributes to arousal state disruption by opioids.
authors: Department of Anesthesia, The Pennsylvania State University, College of Medicine, Hershey 17033-0850, USA.
authors: S
authors: S
authors: Mortazavi
authors: J
authors: J
authors: Thompson
authors: H A
authors: HA
authors: Baghdoyan
authors: R
authors: R
authors: Lydic
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002415:Cats; D005283:Fentanyl / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D009270:Naloxone; D009020:Morphine; D000109:Acetylcholine; D000077208:Remifentanil; D005283:Fentanyl