Interactions between morphine, scopolamine and nicotine: Schedule-controlled responding in rats

Functional interactions between drugs acting on either opioid or cholinergic systems have been demonstrated for both neurochemical and behavioral measures. This study used schedule-controlled responding and isobolographic analyses to examine interactions between the µ opioid receptor agonist morphine and the muscarinic acetylcholine receptor antagonist scopolamine as well as the nicotinic acetylcholine receptor agonist nicotine. In 8 rats responding under a fixed ratio 5 schedule of food presentation, morphine (3.2-10 mg/kg), scopolamine (0.032-1.0 mg/kg), and nicotine (0.1-1 mg/kg) each dose-dependently decreased responding. Acute injection of scopolamine shifted the morphine dose-response curved leftward and downward and acute injection of morphine shifted the scopolamine and nicotine dose-response curves leftward and downward. The interaction between morphine and nicotine was additive; however, the interaction between morphine and scopolamine was infra-additive or supra-additive, depending on whether scopolamine or morphine was administered first. These results provide quantitative evidence regarding potentially important interactions between drugs acting on either opioid or cholinergic systems, although these interactions are modest and appear to depend on the specific conditions of drug administration.