Valproate effect on gamma-aminobutyric acid release in pars reticulata of substantia nigra: combination of push-pull perfusion and fluorescence histochemistry.

Abstract

To study further the previously demonstrated suppressive in vivo effect of sodium valproate (VPA) on gamma-aminobutyric acid (GABA) release in the preoptic area, we examined GABA neurotransmission in substantia nigra (SN), using the push-pull cannula technique in freely moving ovariectomized rats. To clarify whether the area in the substantia nigra that is actually perfused is pars reticulata, known to receive rich GABAergic input from striatum, we used the retrograde fluorescence tracer fast blue (FB) after each perfusion experiment, applying the tracer through the push-pull cannula. Nigral perfusion with VPA caused significant suppression of local GABA release. This effect was more marked in a subgroup of animals showing retrograde labeled cell bodies in striatum, i.e., animals with a tracer application site and therefore also a perfusion site precisely in pars reticulata. Our data suggest that VPA inhibits GABA release in rat SN as it does in the preoptic area, which may be in agreement with our hypothesis of enhanced GABAergic neurotransmission by VPA, causing suppression of presynaptic GABA release through negative feedback actions on the GABA autoreceptor complex. Furthermore, the combination of push-pull cannula technique and retrograde fluorescence tracer application appears to be an important tool to prove afferent connections of the area actually perfused in neuronal networks.