Details

Autor(en) / Beteiligte

• Saigusa, Tadashi
• Aono, Yuri
• Sekino, Reiko
• Uchida, Takuya
• Takada, Koji
• Oi, Yoshiyuki
• Koshikawa, Noriaki
• Cools, Alexander R.

Titel

In vivo neurochemical evidence that newly synthesised GABA activates GABAB, but not GABAA, receptors on dopaminergic nerve endings in the nucleus accumbens of freely moving rats

Ist Teil von

• Neuropharmacology, 2012-02, Vol.62 (2), p.907-913

Erscheinungsjahr

2012

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• GABA released from accumbal GABAergic interneurons plays an inhibitory role in the regulation of dopamine efflux through GABAB and GABAA receptors located on accumbal dopaminergic nerve endings. The cytosolic newly synthesised GABA alters vesicular GABA levels and, accordingly, the amount of GABA released from the neuron. Therefore, we hypothesised that glutamic acid decarboxylase (GAD) which generates GABA in accumbal GABAergic neurons, at least partly determines the GABA receptor subtype-mediated GABAergic tonus. To (in)validate this hypothesis, in vivo microdialysis was used to study the effects of an intra-accumbal infusion of the GAD inhibitor l-allylglycine (allylglycine) on the accumbal dopamine efflux of freely moving rats. The intra-accumbal infusion of allylglycine (50.0, 250.0 and 500.0 nmol) dose-dependently increased the accumbal dopamine levels. The co-administration of tetrodotoxin (720 pmol) suppressed the allylglycine (500.0 nmol)-induced dopamine efflux. The intra-accumbal infusion of GABAB receptor agonist baclofen (2.5 and 5.0 nmol) inhibited the allylglycine (500.0 nmol)-induced dopamine efflux. The baclofenas effects were counteracted by GABAB receptor antagonist saclofen (10.0 nmol). Neither GABAA receptor agonist (muscimol: 25.0 and 250.0 pmol) nor antagonist (bicuculline: 50.0 pmol) altered the allylglycine (250.0 and 500.0 nmol)-induced dopamine efflux. The present study provides in vivo neurochemical evidence that newly synthesised GABA that exerts an inhibitory tonus on the accumbal dopaminergic activity, acts at the level of GABAB receptors, but not GABAA receptors. The present study also shows that there is an allylglycine-insensitive GABA pool that release GABA exerting an inhibitory control of the accumbal dopaminergic activity, at the level of GABAA receptors. This article is part of a Special Issue entitled aPost-Traumatic Stress Disordera.