The effects of several i.p. administered, centrally active cholinergic agonists and antagonists on the naloxone-induced jumping behavior of morphine tolerant and dependent mice were studied in an effort to differentiate muscarinic and nicotinic modification of the withdrawal jumping behavior. Nicotine, tremorine, oxotremorine, arecoline and physostigmine significantly inhibited jumping, whereas atropine, benzotropine, pempidine and mecamylamine significantly potentiated jumping. Quaternary cholinergic drugs did not modify jumping. These drug effects were obtained generally without an alteration of the amount of naloxone or morphine in the brain. Cholinergic drugs also modified the jumping incidence in mice undergoing abrupt morphine abstinence. It is concluded that the inhibition of withdrawal jumping in morphine dependent mice by both muscarinic and nicotinic agonists and its enhancement by muscarinic and nicotinic antagonists reflect cholinergic modifications of the jumping response by a central mechanism(s).
Bibliographical noteFunding Information:
The authors wish to thank Barbara McAninch, Barbara Hitzemann, and Betty Treadway for assistance in the jumping experiments. This study was supported in part by USPHS Grant MH-17017, and Grant DA-00564. Dr. H.H. Loh is a recipient of a NIMH Research Scientist Development Award, K2-MH-70554. Dr. D.A. Brase is an Interdisciplinary Training Program Fellow under USPHS Grant MH-7082-12.
- Cholinergic agonists
- Cholinergic antagonists
- Narcotic dependence
- Withdrawal jumping