Regional release of 3Hdopamine from rat brain in vitro: effects of opioids on release induced by potassium, nicotine, and L-glutamic acid

Previous studies have suggested that the release of dopamine (DA) in the rat brain may be sensitive to modulation by opioid agents, including the endogenous opioid peptides (enkephalins and endorphins). The present study examined the effects of morphine and the enkephalin analogue D-Ala2-Met5-enkephalinamide (DALA) on the release of radiolabeled DA from superfused slices of rat brain regions. The release of preloaded 3HDA was evoked from slices of the caudate-putamen (CP) by application of potassium (K+), nicotine (NIC), or L-glutamic acid (L-GLU). The release of 3HDA from slices of the nucleus accumbens (NA), olfactory tubercle (OT), and substantia nigra (SN) was evoked by L-GLU. Both K+ and NIC evoked a concentration-related release of 3HDA from CP slices. K+-induced release was only partially dependent on calcium (Ca2+), while NIC-evoked release was completely Ca2+ independent. Neither morphine nor DALA influenced the release of 3HDA evoked by K+ or NIC. L-GLU produced a concentration-dependent release of 3HDA from slices of CP, NA, OT, and SN. In all four brain regions, this release was (a) Ca2+-dependent, (b) strongly inhibited by low concentrations of magnesium (Mg2+), (c) greater than the release evoked by D-GLU, (d) attenuated by the putative L-GLU receptor antagonist glutamic acid diethylester (GDEE), and (e) insensitive to tetrodotoxin (TTX) except in the SN. Morphine produced a significant inhibition of L-GLU-evoked 3HDA release from all four regions. Naloxone, which by itself had no significant effect on the L-GLU-evoked release of 3HDA, blocked the inhibitory effect of morphine on this release in the CP but not in the other regions. Levorphanol and dextrorphan were equipotent in reducing the glutamate-stimulated release of 3HDA from CP slices. DALA had no effect on L-GLU-induced release in any of the brain regions examined. The results indicate that L-GLU provokes regional release of DA by acting at a Mg2+-sensitive glutamate receptor. This release is selectively modified by morphine through a mechanism which is insensitive to naloxone.