Attenuation of morphine withdrawal signs by muscimol in the locus coeruleus of rats.
This study examined the effects of intra-locus coeruleus injection of a gamma-amino-butyric acid type A (GABAA) receptor agonist on naloxone-induced withdrawal signs of morphine-dependent rats. Twenty different withdrawal signs were assessed. The total withdrawal score was calculated and used as an index of withdrawal intensity. The gamma-amino-butyric acid agonist and antagonists were injected 15 and 30 min before naloxone injection, respectively. Muscimol, a GABAA agonist (25, 50, and 100 ng/site), decreased the total withdrawal score in a dose-independent manner, whereas bicuculline (0.367, 3.67, and 36.7 ng/site), a GABAA antagonist, and CGP35348 (48.6 ng/site), a gamma-amino-butyric acid type B antagonist, alone had no effects. On the other hand, muscimol effects were reversed by CGP35348 (48.6 ng/site) but not by bicuculline (36.7 ng/site). It may be concluded that the effects of muscimol were antagonized by gamma-amino-butyric acid type B but not by GABAA receptor antagonists. The mechanism involved seems to be intricate and needs further study.
Mirzaii-Dizgah
Iraj
I
Department of Physiology, School of Medicine, Qom University of Medical Sciences, Qom, Iran.
Karimian
Seyed Morteza
SM
Hajimashhadi
Zahra
Z
Riahi
Esmail
E
Ghasemi
Tayeb
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009021:Morphine Dependence; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D009292:Narcotic Antagonists; D009943:Organophosphorus Compounds; D009118:Muscimol; D009270:Naloxone; C066430:CGP 35348; D001640:Bicuculline