ENDOGENOUS OPIOIDS AND SMOKING - A REVIEW OF PROGRESS AND PROBLEMS

The present report examines efforts to elucidate the role of opioid me chanisms in the reinforcement of smoking. A number of approaches have been used to evaluate nicotine-opioid interactions. Opiate agonists su ch as heroin or methadone have been found to increase cigarette smokin g reliably in humans, and morphine has been shown to increase the pote ncy and efficacy of nicotine in rats. There is also an extensive liter ature documenting the nicotine-stimulated release of endogenous opioid s in various brain regions involved in the mediation of opiate reinfor cement. Blockade studies using opioid antagonists have not been as con clusive. Although animal models have demonstrated commonalities betwee n nicotine withdrawal and the opiate abstinence syndrome, including re versibility by morphine, and although the impact of nicotine on certai n response systems such as respiratory reflexes has clearly been shown to involve opioid mediation, attempts to demonstrate opioid modulatio n for the key indicators of smoking reinforcement-cigarette consumptio n and nicotine self-administration-have been fraught with difficulty. Resolution of the apparent contradictions will require taking into acc ount: (a) the biphasic properties of nicotine-opioid effects at higher doses and anti-opioid effects at lower doses; (b) the contributions o f the opioid receptor populations - mu, kappa, sigma - stimulated at v arious dose levels; (c) the possibility that endogenous-opioid activit y is entrained primarily during the acquisition or re-acquisition of n icotine self-administration; (d) the possibility that the endogenous o pioid response does contribute to nicotine reinforcement but only as a delimited component of the neuroregulatory cascade of nicotine; and ( e) the possibility that opioids contribute primarily to nicotine reinf orcement under special conditions such as stress. Taking these conside rations into account should allow studies on endogenous opioid effects to begin to do justice to the complexity of both smoking behavior and the actions of nicotine. (C) 1998 Elsevier Science Ltd. All rights re served.