ROLE OF DYNORPHIN AND GABA IN THE INHIBITORY REGULATION OF NMDA-INDUCED DOPAMINE RELEASE IN STRIOSOME-ENRICHED AND MATRIX-ENRICHED AREAS OFTHE RAT STRIATUM

Using a new superfusion procedure in vitro, we have previously reporte d that the NMDA-evoked release of newly synthesized H-3-dopamine (DA) was higher in matrix- than in striosome-enriched areas of the rat stri atum. In addition, GABAergic medium-sized spiny neurons were shown to be indirectly involved in this regulation. Since dynorphin and GABA ar e colocalized in a population of medium-sized spiny neurons, the role of dynorphin-containing neurons in the NMDA-evoked release of H-3-DA h as been investigated using the same superfusion procedure on rat stria tal slices. (1) The NMDA (50 mu M, 25 min application)-evoked release of H-3- DA was increased in the presence of naloxone (1 mu M, continuo usly delivered) in both striatal compartments, the overall response be ing more elevated in the striosome-enriched area. (2) The TTX (1 mu M, continuously delivered)-resistant NMDA-evoked responses were also enh anced in the presence of naloxone, but in this case, the disinhibitory effects of naloxone were similar in striosome- and matrix-enriched ar eas. (3) The selective kappa-agonist U-50488 (1 mu M) totally reversed the naloxone-disinhibitory effect on the NMDA-evoked response in the matrix-enriched area, but only partially in the striosome-enriched are a. it also completely prevented the disinhibitory effect of naloxone o n the TTX-resistant NMDA-evoked release of H-3-DA in both compartments . (4) The bicuculline (5 mu M)- and naloxone (1 mu M)-disinhibitory ef fects on the NMDA-evoked release of H-3-DA were additive in the matrix - but not in the striosome-enriched areas. Together, these results ind icate that, under the action of NMDA, in addition to GABA, dynorphin i s released from a population of medium-sized spiny neurons, and that t his opiate peptide inhibits the NMDA-evoked release of DA in both stri atal compartments through a TTX-resistant process. in addition, in the striosome-enriched area, NMDA activates another inhibitory local circ uit that is TTX sensitive and could involve mu-opiate receptors. Final ly, the inhibitory effects mediated by GABA and opioid peptide(s) seem to be segregated in the matrix- but not in the striosome-enriched are as.