Partial inhibition of the abstinence syndrome in morphine tolerant-dependent mice following pharmacological denervation.

Mice were chronically treated with either atropine, methysergide or pentobarbital in order to induce sensitivity changes resulting from adaptative adjustments in the central nervous system (CNS), and to examine the degree of tolerance to and physical dependence on morphine several days after the discontinuation of pretreatments. Subsequently to the chronic blockade of muscarinic or serotonergic receptors, the intensity of tolerance was unaffected, but some manifestations of the abstinence behavior induced by naloxone were reduced in part. This attenuation of the abstinence syndrome in the pretreated mice was reverted by an additional dose of either atropine or methysergide administered a few min before naloxone. Additional experiments with physostigmine or 5-hydroxytryptophan (5-HTP) in morphine-dependent mice yielded results compatible with the hypothesis that morphine physical dependence may be the manifestation of compensatory changes of sensitivity to serotonin and acetylcholine in the CNS. These results do not exclude the participation of other neurotransmitters or neurohormones in morphine dependence.