Role of dynorphin and GABA in the inhibitory regulation of NMDA-induced dopamine release in striosome- and matrix-enriched areas of the rat striatum

Abstract

Using a new superfusion procedure in vitro, we have previously reported that the NMDA-evoked release of newly synthesized 3H-dopamine (DA) was higher in matrix- than in striosome-enriched areas of the rat striatum. In addition, GABAergic medium-sized spiny neurons were shown to be indirectly involved in this regulation. Since dynorphin and GABA are colocalized in a population of medium-sized spiny neurons, the role of dynorphin-containing neurons in the NMDA-evoked release of 3H-DA has been investigated using the same superfusion procedure on rat striatal slices. (1) The NMDA (50 μM, 25 min application)-evoked release of 3H-DA was increased in the presence of naloxone (1 μM, continuously delivered) in both striatal compartments, the overall response being more elevated in the striosome-enriched area. (2) The TTX (1 μM, continuously delivered)-resistant NMDA-evoked responses were also enhanced in the presence of naloxone, but in this case, the disinhibitory effects of naloxone were similar in striosome- and matrix-enriched areas. (3) The selective Κ-agonist U-50488 (1 μM) totally re versed the naloxone-disinhibitory effect on the NMDA-evoked response in the matrix-enriched area, but only partially in the striosome-enriched area. It also completely prevented the disinhibitory effect of naloxone on the TTX-resistant NMDA-evoked release of 3H-DA in both compartments. (4) The bicuculline (5 μM)- and naloxone (1 μM)-disinhibitory effects on the NMDA-evoked release of 3H-DA were additive in the matrix- but not in the striosome-enriched areas. Together, these results indicate that, under the action of NMDA, in addition to GABA, dynorphin is released from a population of medium-sized spiny neurons, and that this opiate peptide inhibits the NMDA-evoked release of DA in both striatal compartments through a TTX-resistant process. In addition, in the striosome-enriched area, NMDA activates another inhibitory local circuit that is TTX sensitive and could involve μ-opiate receptors. Finally, the inhibitory effects mediated by GABA and opioid peptide(s) seem to be segregated in the matrix- but not in the striosome-enriched areas.