The effects of various opiates on the spontaneous release of [3H]dopamine ([3H]DA) continuously formed from [3H]tyrosine has been studied in rat striatal slices. Morphine (5 x 10(-6) M), fentanyl (5 x 10(-8) M) and the tripeptide Tyr-D-Ala-Gly-NH-CH(CH3)CH2-CH(CH3)2 (10(-6) M) were without effect, whereas D-Ala2-Met-enkephalinamide (3 x 10(-7) to 10(-5) M), D-Ala2-D-Leu2-enkephalin (5 x 10(-9) M) and the hexapeptide Tyr-D-Ser-Gly-Phe-Leu-Thr (10(-7) M) enhanced [3H]DA release in vitro. The D-Ala2-Met-enkephalinamide stimulation of [3H]DA release was not accompanied by any increase in [3H]DA synthesis and persisted in the presence of tetrodotoxin (5 x 10(-7) M). Naloxone (5 x 10(-7) M) completely blocked the effect of Tyr-D-Ser-Gly-Phe-Leu-Thre (10(-7) M) on [3H]DA release. However, the opiate antagonist did not affect the action of the hexapeptide or of D-Ala2-Met-enkephalinamide when used at a concentration equal to or lower than the agonist. This suggests that both peptides act on opiate receptors having a low sensitivity to naloxone. According to these various results and to the pharmacological characteristics of the opiates tested as described in peripheral organs or in the brain, it is concluded that opiates acting on delta opiate receptors may presynaptically regulate the release of DA in the striatum.
Animals Corpus Striatum