Methadone's effect on nAChRs--a link between methadone use and smoking?

Methadone is a long-acting opioid agonist that is frequently prescribed as a treatment for opioid addiction. Almost all methadone maintenance patients are smokers, and there is a correlation between smoking habit and use of methadone. Methadone administration increases tobacco smoking, and heavy smokers use higher doses of methadone.

Methadone is a non-competitive antagonist at the α4β2 and α3* nicotinic acetylcholine receptors and an agonist at the α7 nicotinic acetylcholine receptor.

Nicotine-methadone interactions have been studied in human beings and in various experimental settings regarding addiction, reward and pain. Most methadone maintenance treatment patients are smokers, and methadone administration has been shown to increase cigarette smoking. Previous in vitro studies have shown that methadone is a non-competitive antagonist at rat α3β4 nicotinic acetylcholine receptors (nAChR) and an agonist at human α7 nAChRs.

Nicotine-morphine interactions at α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors.

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 α4β2, α7 and α3(⁎) nicotinic acetylcholine receptors.

[Effect of Catechol-O-methyltransferase deficiency on reinforcing effects of cocaine (experimental study)].

Catechol-O-methyltransferase (COMT) remains an important regulatory element in prefrontal cortex dopamine homeostasis. The literature data suggest that individual differences in COMT activity (Val158Met polymorphism) might have indirect downstream effects on the reward system. The aim of the present study was to examine whether COMT deletion affects reinforcing effects of cocaine in mice.

[Effect of alpha-conotoxin MII and its N-terminal derivatives on Ca2+ and Na+ signals induced by nicotine in neuroblastoma cell line SH-SY5Y].

Nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation ofintracellular Ca2+-dependent processes in cells both in normal and pathological states, alpha-Conotoxins isolated from Conus snails venom are a valuable tool for the study of pharmacological properties and functional role of nAChRs. In the present study the alpha-conotoxin MII analogue with the additional tyrosine attached to the N terminus (Y0-MII) was prepared. Also we synthesized analogs with the N-terminal glycine residue labeled with the Bolton- Hunter reagent (BH-MII) or fluorestsein isothiocyanate (FITC-MII).