title: Microdialysis evidence that acetylcholine in the nucleus accumbens is involved in morphine withdrawal and its treatment with clonidine.
abstract: This study used microdialysis to measure changes in extracellular acetylcholine (ACh) content in the nucleus accumbens (NAC) of freely moving rats during acute and chronic morphine treatment, and following naloxone-precipitated withdrawal. Morphine injection (20 mg/kg, i.p.) caused a significant decrease in extracellular ACh which was not apparent after repeated exposure to the opiate for 7 days. Basal recovery of ACh was not altered by chronic morphine treatment. On day 8, after morphine dependence had been established, naloxone caused a large increase in ACh levels accompanied by withdrawal symptoms such as wet dog shakes, diarrhea and teeth-chattering. Pretreatment with clonidine (200 micrograms/kg, i.p.) reduced these withdrawal symptoms and eliminated the ACh response. These results suggest that accumbens ACh is involved in some of the aversive aspects of opiate withdrawal.
authors.affiliation: Department of Psychology, Princeton University, NJ 08544-1010.
authors.forename: P
authors.initials: P
authors.lastname: Rada
authors.forename: E
authors.initials: E
authors.lastname: Pothos
authors.forename: G P
authors.initials: GP
authors.lastname: Mark
authors.forename: B G
authors.initials: BG
authors.lastname: Hoebel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003956:Dialysis / Q000379:methods; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D009270:Naloxone; D009020:Morphine; D003000:Clonidine; D000109:Acetylcholine