Nicotine protects against μ-opioid receptor antagonism by β-funaltrexamine: Evidence for nicotine-induced release of endogenous opioids in brain

Abstract 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 β-funaltrexamine (β-FNA, 2.5 μg), an antagonist which irreversibly alkylates opioid receptors, markedly reduced (66%) morphine analgesia. Subcutaneous administration of nicotine (0.1 mg/kg) prior to β-FNA attenuated (31%) the inhibitory effect of β-FNA on morphine analgesia. These data support our hypothesis that endogenous opioids released by nicotine bind to μ-opioid receptors in brain and protect them against inactivation by β-FNA.