Locus ceruleus discharge characteristics of morphine-dependent rats: effects of naltrexone.
Spontaneous and sensory-evoked discharge was recorded from locus ceruleus (LC) neurons of halothane-anesthetized rats that were chronically administered morphine. LC spontaneous discharge rates of morphine-treated rats were comparable to those of rats chronically administered saline. Administration of 1.0 micrograms morphine (i.c.v.), a dose which completely inhibits LC discharge of morphine-naive rats, had no effect on LC spontaneous discharge of morphine-treated rats, demonstrating that opiate tolerance had developed. Naltrexone, 0.3 and 1.0 microgram i.c.v., produced increases in LC spontaneous discharge rates that were 172 and 166% greater than baseline, respectively. Additionally, naltrexone disrupted LC discharge evoked by repeated sciatic nerve stimulation such that evoked discharge was decreased with respect to tonic discharge, and postactivation inhibition was attenuated. Naltrexone did not alter spontaneous or sensory-evoked LC discharge of rats chronically administered saline indicating that these neuronal effects are specific to opiate withdrawal. Pretreatment of rats with dexamethasone, or with an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF, did not attenuate the effects of naltrexone on LC discharge of morphine tolerant rats. The present study confirms other reports of LC activation associated with antagonist precipitated opiate withdrawal in vivo, and extends these observations by characterizing the disruptive effect of opiate withdrawal on the response of LC cells to phasically presented sensory stimuli, and demonstrating that the withdrawal response is not mediated by release of endogenous CRF.
Valentino
R J
RJ
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Wehby
R G
RG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D008125:Locus Coeruleus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009020:Morphine; D009271:Naltrexone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D019966:Substance-Related Disorders / Q000503:physiopathology*
D009271:Naltrexone; D009020:Morphine