The role of dopamine in withdrawal jumping in morphine dependent rats

The role of dopamine (DA) in precipitated withdrawal jumping was studied in morphine dependent rats. Pretreatment with various dopaminergic agonists induced a dose-dependent increase in naloxone induced jumping. Pimocide totally blocked the facilitatory effect of piribedil while naloxone induced jumping was not dose-dependently decreased. Biochemical measurements revealed that during precipitated withdrawal the level of DA was elevated and the accumulation of 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) after probenecid as well as the level of 3-methoxytyramine in the striatum was reduced. Unilateral inactivation of the caudate by local injection of KCl induced contralateral circling during withdrawal. Additional systemic haloperidol pretreatment did not change the direction of circling while additional apomorphine pretreatment changed the direction to ipsilateral and increased the circling rate highly. These latter as well as the biochemical findings strongly suggest an inhibition of striatal DA-mechanisms during withdrawal. The apparent contradiction of these findings to the above finding showing a facilitatroy role of DA-agonists on jumping is discussed.