Opioid neurotransmission plays a role in rewarding process including the reinforcing actions of nicotine. In the past four decades, a great effort has been exercised to test the effectiveness of nonselective opioid antagonists (mainly naloxone and naltrexone) for smoking cessation. However, both clinical and animal researches have yielded equivocal results. That may be attributable to the fact that opioid receptors have three distinctive subtypes (μ, δ, and κ), functions of which are from complimentary to opposite. Our laboratory studies have used animal models of nicotine self-administration to examine involvement of individual opioid receptor subtypes in the reinforcement of nicotine. Specifically, rats were trained in daily 1-h sessions to press a lever to intravenously self-administer nicotine, and antagonists selective for the three subtypes of opioid receptors were administered prior to the test sessions. Results showed that selective blockade of the μ, but not δ or κ, opioid receptors effectively reduced nicotine self-administration, whereas it produced no effect on food self-administration. These results indicate that activation of the opioid μ, but not δ or κ, receptors is specifically involved in nicotine reinforcement. It is suggested that opioid μ receptor-mediated neurotransmission would be a promising target for developing smoking cessation medication.
Part of the book: Smoking