Elsevier

Neuroscience

Volume 89, Issue 4, April 1999, Pages 1219-1227
Neuroscience

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

https://doi.org/10.1016/S0306-4522(98)00336-4Get rights and content

Abstract

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 μg/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.

Section snippets

Experimental procedures

Experiments were conducted in adherence to the legal requirements of The Netherlands concerning research on laboratory animals, and have been approved by the ethical committee of the Utrecht University.

Initiation of drug self-administration

Animals offered cocaine or ethanol readily initiated drug self-administration (Fig. 2) in that their number of self-infusions was significantly higher than that in animals offered saline (cocaine vs saline: F1,20=108.8, P<0.001; ethanol vs saline: F1,16=11.7, P<0.01). In the cocaine experiments an interaction between treatment and time was present (F4,80=10.4, P<0.001). No difference was obtained between the experiments, i.e. “after the session on day 5” and “before the session on day 6”

Discussion

In the present study the implication of endogenous opioid systems in the dynamics of drug addiction was analysed using an in vivo autoradiographic procedure. The self-administration experiments show that animals without previous experience with the drug or the intravenous self-administration procedure readily learned to self-inject cocaine and ethanol, as their intake was higher than the saline controls. This pattern of intake is consistent with earlier reports on drug self-administration

Conclusions

Endogenous opioid activity in restricted mesocorticolimbic and thalamic areas may be implicated in the dynamics of experimental drug addiction, and in particular in processes underlying drug-induced craving. This involvement may be causally related to the reported decrease in craving and relapse in human alcoholics after treatment with an opioid antagonist.45, 62, 63

Acknowledgements

This research was supported by the Netherlands Organisation for Scientific Research (N.W.O.), Grant 900-551-056. The authors would like to thank Dr Jan Dormans for using the IBAS systems and Dr Leo van Wolfswinkel for programming the necessary software for the self-administration procedure. We would also like to thank Liesbeth van Duinkerken, Henk Spierenburg and Jan Hoekman for their assistance.

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