Attenuation of morphine withdrawal signs by muscimol in the locus coeruleus of rats

Abstract

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.