THE ROLE OF CHOLINERGIC SYSTEMS IN THE EXPRESSION OF MORPHINE-WITHDRAWAL

Both oxotremorine and physostigmine both in doses ranging from 25 to 1 00 mu g/kg produced dose-dependent attenuation of withdrawal jumping a nd potentiation of 'wet dog' shakes, burrowing, hypothermia and body w eight loss precipitated by naloxone (1 mg/kg, i.p.) in morphine-depend ent mice. On the other hand, atropine sulphate (2-20 mg/kg) dose-depen dently attenuated all naloxone precipitated withdrawal symptoms except withdrawal hypothermia which was further potentiated. However, the pe ripherally acting derivative atropine methyl nitrate (2-10 mg/kg) also attenuated all naloxone-induced withdrawal symptoms except jumping, w hich was not significantly modified. Hyoscine (0.2-20 mg/kg) exhibited a biphasic effect on withdrawal jumping. Withdrawal jumping was poten tiated by low and attenuated by high doses of hyoscine. Withdrawal bod y weight loss was dose-dependently attenuated but 'wet dog' shakes, bu rrowing and hypothermia were markedly potentiated by hyoscine. Our res ults suggest that a combination of central muscarinic activation and p eripheral muscarinic blockade can partially ameliorate precipitated mo rphine withdrawal. Differences observed between atropine and hyoscine with regard to their modifying effects on withdrawal symptoms may be e xplained on the basis that the drugs may be acting on the different su bpopulations of the muscarinic receptor or through non-cholinergic sys tems.