Separate brain manipulations double dissociate two motivational mechanisms underlying the rewarding effects of opiates. Lesions of the brain stem tegmental pedunculopontine nucleus block the rewarding properties of morphine in drug-naive, but not in drug-dependent, rats. Neuroleptics (which block the action of the neurotransmitter dopamine) abolished opiate motivational effects in drug-dependent, but not in drug-naive, rats in place conditioning paradigms. This second dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals. Furthermore, neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in food-sated (non-food-deprived), animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the line between deprivation and nondeprivation.