Nicotine protects against mu-opioid receptor antagonism by beta-funaltrexamine: evidence for nicotine-induced release of endogenous opioids in brain.

We have hypothesized that some effects of nicotine are mediated through endogenous opioids. This study was designed to demonstrate in rats that nicotine releases endogenous opioids in brain. In the control group, subcutaneous morphine (8 mg/kg) produced analgesia or antinociception as measured by prolongation of tail flick latency. Intracerebroventricular administration 24 h earlier of beta-funaltrexamine (beta-FNA, 2.5 micrograms), an antagonist which irreversibly alkylates opioid receptors, markedly reduced (66%) morphine analgesia. Subcutaneous administration of nicotine (0.1 mg/kg) prior to beta-FNA attenuated (31%) the inhibitory effect of beta-FNA on morphine analgesia. These data support our hypothesis that endogenous opioids released by nicotine bind to mu-opioid receptors in brain and protect them against inactivation by beta-FNA.