Talka_2013_Eur.J.Pharmacol_701_57

Nicotine and opioids share several behavioral and rewarding properties. Although both opioids and nicotine have their own specific mechanism of action, there is empirical and experimental evidence of interactions between these drugs. We studied receptor-level interactions of nicotine and morphine at alpha4beta2, alpha7 and alpha3() nicotinic acetylcholine receptors. [(3)H]epibatidine displacement was used to determine if morphine binds competitively to nicotinic acetylcholine receptors. Functional interactions of morphine and nicotine were studied with calcium fluorometry and (86)Rb(+) efflux assays. Morphine displaced [(3)H]epibatidine from nicotinic agonist binding sites in all cell lines studied. The Ki values for morphine were 13.2muM in SH-EP1-halpha4beta2 cells, 0.16muM and 126muM in SH-SY5Y cells and 43.7muM in SH-EP1-halpha7 cells. In SH-EP1-halpha4beta2 cells expressing alpha4beta2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of (86)Rb(+) efflux comparable to cytisine (with EC50 values of 53.3muM for morphine and 5.38muM for cytisine). The effect of morphine was attenuated concentration-dependently by the nicotinic antagonist mecamylamine. In the SH-SY5Y cell line expressing several subtypes of nicotinic acetylcholine receptors morphine had an inhibitory effect on nicotine induced (86)Rb(+) ion efflux mediated by alpha3() nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at alpha4beta2 nicotinic acetylcholine receptors and as a weak antagonist at alpha3() nicotinic acetylcholine receptors.