The Role of Dopamine in the Expression of Morphine Withdrawal

Abstract

1. Both L-dopa and low doses of apomorphine potentiated withdrawal symptoms such as jumping,“wet dog” shakes and burrows. L-dopa reduced hypothermia and potentiated body weight loss, whereas apomorphine produced opposite effects. 2. Higher doses of apomorphine attenuated jumping and burrows but had no effect on “wet dog” shakes. On the other hand, and with the exception of sulpiride, all other dopamine (DA) antagonists produced effects opposite those of the agonists with regard to jumping, “wet dog” shakes and burrows. 3. In addition, DA antagonists reduced hypothermia and body weight loss. The effects of DA agonists and antagonists were investigated in mice injected with 6-hydroxydopamine (6-OHDA) intracerebrally to examine whether DA-mediated effects are somehow linked to noradrenergic pathways. 4. Mice pretreated with 6-OHDA developed a higher degree of naloxone-induced withdrawal jumping than did untreated mice. 6-OHDA reversed the effects of apomorphine on “wet dog” shakes and burrows while abolishing those of L-dopa on all withdrawal symptoms, the only exception being jumping, which remained unchanged. 5. 6-OHDA also reversed the effects of sulpiride on all withdrawal symptoms while reversing the effects of pimozide on jumping, and it abolished its effect on hypothermia. 6. These findings provide evidence suggesting that the effects of DA agonists and antagonists are dependent at least partly on intact noradrenergic pathways.