Inhibitory control of the gabaergic transmission in the rat neostriatum byD-2 dopamine receptors

The aim of the study was to determine the role of dopamine on the GABAergic input to striatal projection neurons. Accordingly, the effect of the activ ation of dopamine D-2-like receptors on GABA-mediated depolarizing postsyna ptic potentials evoked in striatal slices by local stimulation was studied. Conventional intracellular recording techniques were used to record the sy naptic responses. The experiments were done in the presence of 6-cyano-7-ni troquinoxaline-2,3-dione (20 mu M) and (+/-)-2-amino-5-phosphonovaleric aci d (40 mu M) to block the participation of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropoinate/kainate and N-methyl-D-aspartate receptors in the synap tic response. The GABAergic nature of the response was assessed by its pote ntiation by pentobarbital (50 mu M) and by its elimination by bicuculline o r picrotoxin, At 100 nM, a concentration already maximal, dopamine inhibite d by 55% the GABAergic synaptic response. The inhibitory effect was totally blocked by the selective antagonist of D2-like receptors, sulpiride (100 n M). The dopamine inhibition was observed only in one-third of the studied n eurons and was concentration dependent (IC50 = 14 nM). The inhibition was n ot associated with changes in the input resistance or any other membrane pr operty. In addition, dopamine (50 nM) reduced the frequency but not the amp litude of spontaneous, bicuculline-sensitive depolarizing postsynaptic pote ntials. The D2-like receptor agonist quinpirole also dose-dependently (IC50 = 10 nM) inhibited the GABAergic synaptic response. As with dopamine, the inhibition did not change the membrane properties of the studied neurons. I n addition, the quinpirole induced inhibition of the GABA response was acco mpanied by increased paired-pulse facilitation. The results indicate that D-2-like receptors located on intrinsic GABAergic terminals in the rat striatum exert an inhibitory control of the GABAergic input to striatal projection neurons. The dopaminergic effect would be tra nslated in facilitation of the firing of the neurons upon the arrival of th e cortical input. (C) 1999 IBRO. Published by Elsevier Science Ltd.