Kavalactones and Dihydrokavain Modulate GABAergic Activity in a Rat Gastric-Brainstem Preparation

Abstract

Using an in vitro neonatal rat gastric-brainstem preparation, the activity of majority neurons recorded in the nucleus tractus solitarius (NTS) of the brainstem were significantly inhibited by GABA_A receptor agonist, muscimol (30 μM), and this inhibition was reversed by selective GABA_A receptor antagonist, bicuculline (10 μM). Application of kavalactones (300 μg/ml) and dihydrokavain (300 μM) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (39 % and 32 %, respectively, compared to the control level), and this reduction was partially reversed by bicuculline (10 μM). Kavalactones or dihydrokavain induced inhibitory effects were not reduced after co-application of saclofen (10 μM; a selective GABA_B receptor antagonist) or naloxone (100 nM; an opioid receptor antagonist). Pretreatment with kavalactones (300 μg/ml) or dihydrokavain (300 μM) significantly decreased the NTS inhibitory effects induced by muscimol (30 μM), approximately from 51 % to 36 %. Our results demonstrated modulation of brainstem GABAergic mechanism by kavalactones and dihydrokavain, and suggested that these compounds may play an important role in regulation of GABAergic neurotransmission.