Naltrexone affects cocaine self-administration in naive rats through the ventral tegmental area rather than dopaminergic target regions

Behavioural studies have shown an involvement of central endogenous opioid systems in experimental cocaine addiction. Seeking to further localize the attenuating effect of opioid blockade on the reinforcing effects of cocaine , naltrexone was administered locally to different regions of the mesocorti colimbic system, which are thought to be critically involved in cocaine sel f-administration behaviour. Both cell body and nerve terminal regions of th is system were targeted. Using a model for the initiation of cocaine self-a dministration behaviour, no effect of naltrexone was found in caudate, amyg daloid or accumbens nuclei, nor in the medial prefrontal cortex. However, b lockade of endogenous opioid receptors in the ventral tegmental area region attenuated cocaine self-administration With the initiation model, this fin ding reflects an attenuating effect on the reinforcing effects of cocaine. The attenuation of self-administration was dependent on the naltrexone dose . The present findings suggest that endogenous opioid systems in the ventra l tegmental area modulate the reinforcing efficacy of cocaine. (C) 1999 Els evier Science B.V./ECNP. All rights reserved.