Morphine-naloxone interactions: a role for nonspecific morphine excitatory effects in withdrawal

The opiate antagonist naloxone precipitates withdrawal when given either 15 minutes after or 1 minute before a single injection of morphine in drug-naïve mice. We propose that withdrawal signs arise from a synergistic mixture of excitatory influences that are direct (agonistic action on nonspecific opiate receptors) and indirect (sensory and affective disorders, stress, hormonal and neurotransmitter dysfunction, and so forth). The predominant effects during precipitated withdrawal are assumed to be direct, whereas during abstinence in tolerant animals they are indirect.