Blockade of gamma-aminobutyric acid-receptors of the B-subtype inhibits the dopamine-induced enhancement of the release of cholecystokinin-like immunoreactivity from slices of rat dorsal caudatoputamen.

Abstract

When slices of rat dorsal caudatoputamen (= neostriatum) are incubated in vitro, cholecystokinin-like immunoreactivity (CCK-LI) is released upon addition of veratridine (3.75 mumol/l). This release is affected by dopamine and by gamma-aminobutyric acid (GABA)-receptor agonists. Dopamine enhances the release by stimulating dopamine D2-receptors and decreases it via D1-receptors. GABAA-receptor agonists enhance the veratridine-induced release of CCK-LI, while GABAB-receptor agonists decrease it. In the present investigation, it was examined whether GABA-receptors are involved in the effect which dopamine exerts via D2-receptors. The GABAA-receptor antagonist bicuculline (10 mumol/l) and the blocker of the GABAA-receptor ionophore picrotoxin (1 mumol/l) did not affect the dopamine (0.1 mumol/l)-induced increase in the release of CCK-LI. However, the GABAA-receptor agonist muscimol (1 mumol/l) not only enhanced the release of CCK-LI, but also prevented a further enhancement by dopamine (0.1 mumol/l). This effect of muscimol was blocked by bicuculline (10 mumol/l). In the presence of delta-amino-n-valeric acid (0.1 mmol/l), which has been described to block GABAB-receptors, dopamine no longer enhanced the veratridine-induced release of CCK-LI. delta-Amino-n-valeric acid also inhibited the pronounced enhancement of the release of CCK-LI caused by dopamine (0.1 mumol/l and 1 mumol/l in the presence of the preferential D1-receptor antagonist SCH 23390. The effect of delta-amino-n-valeric acid persisted in the presence of bicuculline (10 mumol/l and 100 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)