CHARACTERIZATION OF METHIONINE-ENKEPHALIN RELEASE IN THE RAT STRIATUMBY IN-VIVO DIALYSIS - EFFECTS OF GAMMA-HYDROXYBUTYRATE ON CELLULAR AND EXTRACELLULAR METHIONINE-ENKEPHALIN LEVELS
S. Gobaille et al., CHARACTERIZATION OF METHIONINE-ENKEPHALIN RELEASE IN THE RAT STRIATUMBY IN-VIVO DIALYSIS - EFFECTS OF GAMMA-HYDROXYBUTYRATE ON CELLULAR AND EXTRACELLULAR METHIONINE-ENKEPHALIN LEVELS, Neuroscience, 60(3), 1994, pp. 637-648
The opioid 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 conc
erning the dopaminergic nigrostriatal pathway, which is closely linked
to the expression of enkephalins in the striatum. In the present stud
y, 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 decreas
e in the extracellular release of met-enkephalin. In parallel, a dose-
and time-dependent gammahydroxybutyrate-induced accumulation of met-e
nkephalin in striatum was observed. These two phenomena (tissue accumu
lation and inhibition of release) were blocked by NCS-382, a gamma-hyd
roxybutyrate receptor antagonist. The striatal met-enkephalin accumula
tion does not seem to be exclusively due to the inhibition of its rele
ase. Thus, a gamma hydroxybutyrate mediating effect on met-enkephalin
synthesis is suggested, most probably occurring via functional modulat
ion of striatal dopamine synthesis and release. To understand the role
of this dopaminergic mechanism, unilateral lesions of the nigrostriat
al dopaminergic pathway were carried out. In gamma-hydroxybutyrate-tre
ated rats, striata exhibited a similar increase in met-enkephalin cont
ent. In untreated rats, only the lesioned striatum showed an identical
increase in met-enkephalin levels. Thus, striatal met-enkephalin accu
mulation could be attributed to the suppression of the dopaminergic im
pulse flow, due to gamma-hydroxybutyrate or to the action of 6-hydroxy
dopamine. In the extracellular spaces (microdialysis experiments), gam
ma-hydroxybutyrate administration induced identical modifications of m
et-enkephalin release in lesioned or non-lesioned striata. These modif
ications could be reproduced by peripheral or striatal administration
of sulpiride, a D-2/D-3 antagonist. From a functional point of view, t
he dopaminergic D-2 receptor blockade or the gamma-hydroxybutyrate-ind
uced inhibition of dopamine release could be considered to induce simi
lar results, with identical consequences on striatal met-enkephalin ac
cumulation and release. These results suggest that gamma-hydroxybutyra
te-induced modifications in met-enkephalin release, presumably potenti
ated by 6-hydroxydopamine treatment, act via a functional modification
of the nigrostriatal dopaminergic pathway.