title: Characterization of methionine-enkephalin release in the rat striatum by in vivo dialysis: effects of gamma-hydroxybutyrate on cellular and extracellular methionine-enkephalin levels.
abstract: The opioïd system is implicated in mediating the effects produced upon administration of gamma-hydroxybutyrate. Gamma-hydroxybutyrate occurs endogenously in the mammalian brain, and is most probably involved in the regulation of some basic brain functions, particularly those concerning the dopaminergic nigrostriatal pathway, which is closely linked to the expression of enkephalins in the striatum. In the present study, in vivo microdialysis was used to examine the basic characteristics of methionine-enkephalin (met-enkephalin) release in the striatum of Wistar rats, using a high performance radioimmunoassay. Administration of gamma-hydroxybutyrate to the rats induced a dose-dependent decrease in the extracellular release of met-enkephalin. In parallel, a dose- and time-dependent gamma-hydroxybutyrate-induced accumulation of met-enkephalin in striatum was observed. These two phenomena (tissue accumulation and inhibition of release) were blocked by NCS-382, a gamma-hydroxybutyrate receptor antagonist. The striatal met-enkephalin accumulation does not seem to be exclusively due to the inhibition of its release. Thus, a gamma-hydroxybutyrate mediating effect on met-enkephalin synthesis is suggested, most probably occurring via functional modulation of striatal dopamine synthesis and release. To understand the role of this dopaminergic mechanism, unilateral lesions of the nigrostriatal dopaminergic pathway were carried out. In gamma-hydroxybutyrate-treated rats, striata exhibited a similar increase in met-enkephalin content. In untreated rats, only the lesioned striatum showed an identical increase in met-enkephalin levels. Thus, striatal met-enkephalin accumulation could be attributed to the suppression of the dopaminergic impulse flow, due to gamma-hydroxybutyrate or to the action of 6-hydroxydopamine. In the extracellular spaces (microdialysis experiments), gamma-hydroxybutyrate administration induced identical modifications of met-enkephalin release in lesioned or non-lesioned striata. These modifications could be reproduced by peripheral or striatal administration of sulpiride, a D2/D3 antagonist. From a functional point of view, the dopaminergic D2 receptor blockade or the gamma-hydroxybutyrate-induced inhibition of dopamine release could be considered to induce similar results, with identical consequences on striatal met-enkephalin accumulation and release. These results suggest that gamma-hydroxybutyrate-induced modifications in met-enkephalin release, presumably potentiated by 6-hydroxydopamine treatment, act via a functional modification of the nigrostriatal dopaminergic pathway.
authors.affiliation: Centre de Neurochimie, UPR 416 CNRS, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Gobaille
authors.forename: C
authors.initials: C
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Cupo
authors.forename: F
authors.initials: F
authors.lastname: Herbrecht
authors.forename: M
authors.initials: M
authors.lastname: Maitre
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001567:Benzocycloheptenes / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis; D004744:Enkephalin, Methionine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects; D012978:Sodium Oxybate / Q000494:pharmacology*; D013469:Sulpiride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D001567:Benzocycloheptenes; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; C066471:NCS 382; D013779:Tetrodotoxin; D004744:Enkephalin, Methionine; D014701:Veratridine; D012978:Sodium Oxybate; D013469:Sulpiride; D016627:Oxidopamine; D004298:Dopamine