Destruction of the locus coeruleus decreases physical signs of opiate withdrawal.
The purpose of the present study was to investigate the role of the locus coeruleus in the development of opiate dependence. Two groups of rats each were subjected to either a electrolytic lesion of the locus coeruleus or a sham lesion. All animals were implanted with an intracerebroventricular (i.c.v.) cannula, and made physically dependent by subcutaneous insertion of two 75-mg morphine (base) pellets. Abstinence was precipitated by i.c.v. administration of methylnaloxonium (31-1,000 ng) 72 h after pellet implantation. Methylnaloxonium administered intracerebroventricularly induced a withdrawal syndrome characterized by the appearance of teeth chattering, mastication, rearing, wet dog shakes, jumping, piloerection, hyperactivity, ptosis and eye twitch. Withdrawal observed in the electrolytic lesion groups was less severe than in sham group. The presence of mastication, rearing, piloerection, hyperactivity, ptosis and eye twitch was significantly lower. These results support the hypothesis that the locus coeruleus has an important role in the expression of the physical signs of opiate dependence.
Maldonado
R
R
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Koob
G F
GF
D000818:Animals; D001763:Blepharoptosis / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005133:Eye Movements / Q000187:drug effects; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008409:Mastication / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010863:Piloerection / Q000187:drug effects; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D000644:Quaternary Ammonium Compounds; D009270:Naloxone; C041269:N-methylnaloxone; D009020:Morphine; D009638:Norepinephrine