diprenorphine and Alcoholism

The importance of the opioid receptor system in substance dependence is increasingly recognised. We used PET with the non-selective tracer [11C]diprenorphine to examine opioid receptor binding in early abstinence from alcohol dependence and the relationship to craving. We recruited 11 alcohol dependent patients and 13 controls. Subjects underwent one [11C]diprenorphine PET scan in early abstinence from dependent alcohol use (approximately 2 weeks) and 2 months later if continuously abstinent. Global and regional [11C]diprenorphine volumes of distribution (VD) were increased in alcohol dependent patients compared with controls but did not reach significance. We demonstrated a correlation between global and regional [11C]diprenorphine VD and craving in alcohol dependent patients which persisted in the anterior cingulate cortex into extended abstinence. This confirms previous work showing increased opioid receptor availability in early abstinence from substances of abuse and correlation with craving suggesting that the opioid system plays a fundamental role in this phase of addiction.

Topics: Adult; Alcoholism; Behavior, Addictive; Brain; Carbon Isotopes; Case-Control Studies; Diprenorphine; Humans; Male; Middle Aged; Narcotic Antagonists; Positron-Emission Tomography; Radioligand Assay; Receptors, Opioid; Substance Withdrawal Syndrome

Endogenous opioids have been implicated in the neurobiological mechanisms underlying drug addiction. Although some information is available concerning effects of abused drugs on the endogenous opioid systems, the interpretation of these effects is hampered because data on the actual changes in the endogenous opioids during the dynamics of the drug addiction are lacking. The present report deals with changes in endogenous opioid activity before and after the daily self-administration session in rats offered cocaine or ethanol, using an in vivo autoradiographic receptor occupancy procedure. In separate saline-controlled experiments drug-naive rats were allowed to intravenously self-administer cocaine (30 microg/infusion) and ethanol (0.05%) for five consecutive daily sessions of 6 h. Immediately following the last session on day 5 or just before a scheduled next daily session on day 6, the rats were injected with [3H]diprenorphine and subsequently prepared for autoradiography. Decreased [3H]diprenorphine binding was observed throughout the subcortical brain after the daily session in cocaine, but hardly in animals self-administering ethanol. These changes are thought to reflect a direct or an indirect effect of the drug on endogenous opioid systems. Before the daily session, the [3H]diprenorphine binding was decreased in restricted areas of the mesocorticolimbic system and of the thalamus in both cocaine and ethanol self-administering animals. These data suggest that release of endogenous opioids at the time the desire for cocaine or ethanol is high, which may be pertinent for drug-induced craving and relapse of drug addicts.

Topics: Alcoholism; Animals; Autoradiography; Brain; Cocaine; Cocaine-Related Disorders; Diprenorphine; Endorphins; Ethanol; Infusions, Intravenous; Limbic System; Male; Organ Specificity; Rats; Rats, Wistar; Self Administration; Thalamus; Tritium

We have tested whether the opioid antagonists naloxone (2 mg/kg), naltrexone (2 mg/kg) and diprenorphine (0.2 mg/kg), and the agonist morphine (4-8 mg/kg) given subcutaneously (10 min before ethanol for 7 days) modify the ethanol withdrawal syndrome (audiogenic seizures) following chronic ethanol intoxication in rats. We found that naloxone, naltrexone and diprenorphine modified the ethanol withdrawal syndrome. These findings do not rule out the possibility of a biochemical link between the action of ethanol and opiates at the level of opioid receptors.

Topics: Alcoholism; Animals; Diprenorphine; Female; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Inbred Strains; Receptors, Opioid; Seizures; Substance Withdrawal Syndrome