Physiological and behavioral approaches to the study of the quasi-morphine withdrawal syndrome.

The effects of two benzazocines, UM-1037 and UM-1046, which produce a quasi-morphine abstinence syndrome in normal rhesus monkeys, were characterized by the use of the isolated guinea-pig ileal preparation and by a drug discrimination procedure in pigeons. These benzazocines produce a contraction of the ileum isolated from narcotic-naive guinea pigs similar to the narcotic antagonist-precipitated contraction of ilea isolated from morphine-pretreated animals. This effect is suppressed by morphine, and the suppression is reversed by naloxone. These benzazocines appear to stimulate the release of acetylcholine from ilea that have not been exposed to narcotics, and thus produce an effect similar to the release of acetylcholine produced by narcotic antagonists in ilea that have been exposed to morphine-like narcotics. The drug discrimination studies are also consistent with the involvement of cholinergic mechanisms in the behavioral effects produced by the benzazocines. In pigeons that have been trained to discriminate UM-1046 from saline, physostigmine, but not neostigmine, produces responses like those produced by UM-1046. In contrast, drugs from other pharmacological classes do not share discriminative stimulus properties with UM-1046. Thus, complementary evidence was obtained from both a physiological and a behavioral approach. The involvement of cholinergic pathways in the quasi-abstinence syndrome produced by UM-1037 and UM-1046 suggests that similar pathways might be active during narcotic abstinence.