INCREASED OPIOID INHIBITION OF GABA RELEASE IN NUCLEUS-ACCUMBENS DURING MORPHINE-WITHDRAWAL

The nucleus accumbens is a key component of the reward pathway that pl ays a role in addiction to many drugs of abuse, including psychostimul ants and opioids, The effects of withdrawal from chronic morphine were examined in the nucleus accumbens using brain slices from morphine-tr eated animals. Recordings were made from interneurons in the shell of nucleus accumbens, and the presynaptic inhibition of GABA-A IPSCs by o pioids was examined. In slices from control animals, opioids caused a maximal inhibition of 50%, forskolin increased the IPSC amplitude by l ess than twofold, and the maximal inhibition by opioids in the presenc e of forskolin was not changed. During withdrawal, however, forskolin caused approximately a fourfold increase in the amplitude of the IPSC, and the maximal inhibition by opioids was increased to 80%, The resul ts indicate that transmitter release is increased during opioid withdr awal, particularly after the activation of adenylyl cyclase. The cAMP- dependent increase in transmitter release is potently inhibited by opi oids, such that the overall effect of opioids is augmented during with drawal. The induction of an opioid-sensitive cAMP-dependent mechanism that regulates transmitter release may be a critical component of acut e opioid withdrawal.