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

Abstract

1. 1. The effects exerted by GABA B 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. The selective GABA B receptor agonist, baclofen, at concentration of 5 × 10 −9- 1 × 10 −8-5 × 10 −8 M was able to reduce dose-dependently the naloxone-induced contracture after exposure to μ (Morphine and Dago) and k (U50–488H) opiate agonists. 4. 4. Pretreatment with phaclofen (5 × 10 9-1 × 10 8-5 × 10 −8 M), a selective GABAβ receptor antagonist, inhibited dose dependently baclofen antagonism on responses to both μ and k agonists. 5. 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.