Role of dynorphin and GABA in the inhibitory regulation of NMDA-induced dopamine release in striosome- and matrix-enriched areas of the rat striatum.
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 microM, 25 min application)-evoked release of 3H-DA was increased in the presence of naloxone (1 microM, continuously delivered) in both striatal compartments, the overall response being more elevated in the striosome-enriched area. (2) The TTX (1 microM, 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 kappa-agonist U-50488 (1 microM) totally reversed 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 microM)- and naloxone (1 microM)-disinhibitory effects on the NMDA-evoked release of 3H-DA were additive in the matrix- but not in the striosome-enriched areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Krebs
M O
MO
Chaire de Neuropharmacologie, INSERM U114, Collège de France, Paris.
Gauchy
C
C
Desban
M
M
Glowinski
J
J
Kemel
M L
ML
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004399:Dynorphins / Q000502:physiology*; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014316:Tritium; D009270:Naloxone; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D004298:Dopamine; D001640:Bicuculline