The present proposal seeks to establish a role for the endogenous opioid system in nicotine and alcohol dependence by evaluating the ability of an opioid antagonist naloxone, to precipitate withdrawal symptoms, similar to those seen in opiate withdrawal, in male and female, alcohol and nicotine dependent individuals and normal subjects. Subjects will be challenged with 2, separate doses of naloxone or placebo and observed for signs and symptoms of opiate withdrawal, as well as changes in craving for alcohol and nicotine. In individuals who are co-dependent on both alcohol and nicotine, the severity of alcohol dependence has been found to be correlated with both tobacco use and the severity of nicotine dependence. This proposal will establish that both nicotine and alcohol dependence involve alterations in the endogenous opioid system, which contributes to severity of dependence.
The specific aims of the proposal are: 1) To determine whether the opioid antagonist naloxone precipitates a withdrawal syndrome in nicotine dependent individuals; 2) to determine whether naloxone precipitates a withdrawal syndrome in alcoholics; 3) to determine if the naloxone-precipitated withdrawal syndrome is different for men and women; 4) to evaluate the severity of withdrawal in individuals who are co-dependent on alcohol and nicotine; and 5) to model neuroendocrine changes during naloxone-precipitated withdrawal. If our hypotheses regarding an opioid involvement in alcohol and nicotine dependence are confirmed, this paradigm could be used to quantitate degree of dependence on, and develop targeted prevention strategies for, alcohol and nicotine dependence.
| Krishnan-Sarin, S; Rosen, M I; O'Malley, S S (1999) Naloxone challenge in smokers. Preliminary evidence of an opioid component in nicotine dependence. Arch Gen Psychiatry 56:663-8 |
