Effect of naloxone on dopamine uptake and release in vitro in the striatum

The opiate antagonist naloxone (NX) can inhibit the stereotyped behavior elicited by the directly acting dopamine (DA) agonist apomorphine, while potentiating the same behavior induced by amphetamine, an indirect DA agonist. Since NX does not appear to bind to striatal 3H-DA receptors, these effects may be mediated by an indirect action exerted by naloxone on the nigrostriatal pathway. To confirm this, the effect of NX on DA uptake in striatal homogenates was assessed in vitro, and also the effect of NX on DA release in both striatal synaptosomes and slices. While NX had no effect on its own in either of these preparations, it was able to significantly enhance the release of DA induced by d-amphetamine. Since NX has no effect by itself on either behavior or DA release, it appears that NX can exert an active effect on the release of striatal DA only if the nigrostriatal pathway is in a state of arousal (e.g. by amphetamine).