Endogenous opioids implicated in the dynamics of experimental drug addiction: An in vivo autoradiographic analysis

Endogenous opioids have been implicated in the neurobiological mechanisms u nderlying drug addiction. Although some information is available concerning effects of abused drugs on the endogenous opioid systems, the interpretati on of these effects is hampered because data on the actual changes in the e ndogenous opioids during the dynamics of the drug addiction are lacking. Th e present report deals with changes in endogenous opioid activity before an d after the daily self administration session in rats offered cocaine or et hanol, using an in vivo autoradiographic receptor occupancy procedure. In s eparate saline-controlled experiments drug-naive rats were allowed to intra venously self-administer cocaine (30 mu g/infusion) and ethanol (0.05%) for five consecutive daily sessions of 6 h. Immediately following the last ses sion on day 5 or just before a scheduled next daily session on day 6, the r ats were injected with [H-3]diprenorphine and subsequently prepared for aut oradiography. Decreased [H-3]diprenorphine binding was observed throughout the subcortical brain after the daily session in cocaine, but hardly in ani mals self-administering ethanol. These changes are thought to reflect a dir ect or an indirect effect of the drug on endogenous opioid systems. Before the daily session, the [H-3]diprenorphine binding was decreased in restrict ed areas of the mesocorticolimbic system and of the thalamus in both cocain e and ethanol self-administering animals. These data suggest that release of endogenous opioids at the time the desir e for cocaine or ethanol is high, which may be pertinent for drug-induced c raving and relapse of drug addicts. (C) 1999 IBRO. Published by Elsevier Sc ience Ltd.