Gabab receptors are involved in the control of acute opiate withdrawal in isolated tissue

1. The effects exerted by GABA(B) 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 morphine (less selective mu agonist), DAGO (highly selective mu agonist) and U50-488H (highly selective k agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3, The selective GABA(B) receptor agonist, baclofen, at concentration of 5 x 10(-9)-1 x 10(-8)-5 x 10(-8) M was able to reduce dose-dependently the naloxone-induced contracture after exposure to mu (morphine and DAGO) and k (U50-488H) opiate agonists. 4. Pretreatment with phaclofen (5 x 10(-9)-1 x 10(-8)-5 x 10(-8) M), a selective GABAB receptor antagonist, inhibited dose dependently baclofen antagonism on responses to both mu and k agonists. 5. The results of our experiments indicate that GABA(B) receptors are involved in the control of opiate withdrawal in vitro, confirming an important functional interaction between the GABAergic system and opioid withdrawal.