GABA(A) RECEPTOR ANTAGONISTS REDUCE ACUTE OPIATE WITHDRAWAL IN ISOLATED TISSUE

1. The effect exerted by GABA(A) receptor agonists and antagonists on the acute opiate withdrawal induced by mu and k receptor agonists were investigated in vitro. 2. Following a 4 min in vitro exposure to morp hine (less selective mu agonist), DAGO (highly selective mu agonist) a nd U50-488H (highly selective k agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3. Bic uculline (1x10(-5)-5x10(-5)-1x10(-4) M), a GABA(A) receptor antagonist , injected 10 min before or after the opioid agonists was able dose-de pendently to antagonize the naloxone-induced contracture after exposur e to mu (morphine and DAGO) and k (U50-488H) opiate agonists. 4. Furth ermore, picrotoxin (1x10(-5)- 5x10(-5)-1x10(-4) M), an antagonist of G ABA-linked chloride channels, was able to exert the same effects. 5. M uscimol (1x10(-5)-5x10(-5)-1x10(-4) M), a GABA(A) receptor agonist, wa s able to increase dose dependently both mu and k opiate withdrawal. 6 . The data indicate that both GABA(A) receptor agonists and antagonist s are able to control opiate withdrawal in vitro suggesting an importa nt functional interaction between GABAergic system and the opioid with drawal both at the mu and k receptor level.