Morphine and δ-opiate agonists locally stimulate in vivo dopamine release in cat caudate nucleus

Abstract

The peripheral administration of morphine^1–4 or the intraventricular injection of either Met-enkephalin or D-Ala²-Met-enkephalinamide⁴ (a synthetic enkephalin analogue resistant to enzyme degradation) enhanced dopamine (DA) turnover in the rat striatum. These effects, in turn, could be blocked by the opiate antagonist naloxone^1,4. As the striatum contains a high density of opiate receptors⁵, these drugs may be affecting DA metabolism by a local action. This hypothesis is supported by the evidence that morphine still enhanced striatal DA turnover shortly after transection of the nigro-striatal DA pathway⁶. Furthermore, D-Ala²-Met-enkephalinamide directly injected into the striatum significantly increased striatal DA turnover⁴. However, the mechanism by which opiates stimulate DA turnover is not clear because they have not yet been shown to enhance DA outflow in in vitro release studies^7–9. We have therefore now examined in vivo the local effects of opiates on the release of DA in the cat caudate nucleus. We find that both morphine and more markedly, D-Ala²-Met-enkephalinamide stimulate DA release. The action of morphine is antagonized by naloxone, but that of the synthetic enkephalin is not. Because the effects of D-Ala²-Met-enkephalinamide are similar to those of the peripheral δ-receptor agonist Tyr-D-Ser-Gly-Phe-Leu-Thr, we conclude that the synthetic enkephalin acts on δ-receptors.