GABA A receptor antagonists reduce acute opiate withdrawal in isolated tissue

Abstract

1. 1. The effect exerted by GABA, receptor agonists and antagonists on the acute opiate withdrawal induced by μ and k receptor agonists were investigated in vitro. 2. 2. Following a 4 min in vitro exposure to morphine (less selective μ agonist), DAGO (highly selective μ agonist) and U50-488H (highly selective k agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3. 3. Bicuculline (1 × l0 5 − 5 × l0 −5 − 1 × l0 4M), a GABA A receptor antagonist, injected 10 min before or after the opioid agonists was able dose-dependently to antagonize the naloxone-induced contracture after exposure to p (morphine and DAGO) and k (U50-488H) opiate agonists. 4. 4. Furthermore, picrotoxin (1 × l0 5 − 5 × l0 −5 − 1 × l0 4M) ,an antagonist of GABA-linked chloride channels, was able to exert the same effects. 5. 5. Muscimol (1 × l0 5 − 5 × l0 −5 − 1 × l0 4M), a GABA A receptor agonist, was able to increase dose dependently both μ. and k opiate withdrawal. 6. 6. The data indicate that both GABA A receptor agonists and antagonists are able to control opiate withdrawal in vitro suggesting an important functional interaction between GABAergic system and the opioid withdrawal both at the μ. and k receptor level.