Naltrexone affects cocaine self-administration in naïve 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 mesocorticolimbic system, which are thought to be critically involved in cocaine self-administration behaviour. Both cell body and nerve terminal regions of this system were targeted. Using a model for the initiation of cocaine self-administration behaviour, no effect of naltrexone was found in caudate, amygdaloid or accumbens nuclei, nor in the medial prefrontal cortex. However, blockade of endogenous opioid receptors in the ventral tegmental area region attenuated cocaine self-administration. With the initiation model, this finding 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 ventral tegmental area modulate the reinforcing efficacy of cocaine.