Blockade of ?-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

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Abstract
When slices of rat dorsal caudatoputamen (= neostriatum) are incubated in vitro, Choecystokinin-like immunoreactivity (CCK-LI) is released upon addition of veratridine (3.75 μmol/l). This release is affected by dopamine and by γ-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 μmol/l)and the blocker of the GABAA-receptor ionophore picrotoxin (1 μmol/l) did not affect the dopamine (0.1 μmol/1)-induced increase in the release of CCK-LI. However, the GABAA-receptor agonist muscimol (1 μmol/l) not only enhanced the release of CCK-LI, but also prevented a further enhancement by dopamine (0.1 μmol/l). This effect of muscimol was blocked by bicuculline (10 μmol/l). In the presence of δ-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. δ-Amino-n-valeric acid also inhibited the pronounced enhancement of the release of CCK-LI caused by dopamine (0.1 μmol/l) and 1 μmol/l in the presence of the preferential D1-receptor antagonist SCH 23390. The effect of δ-amino-n-valeric acid persisted in the presence of bicuculline (10 μmol/l and 100 μmol/l). (+)-Baclofen, a partial agonist at GABAB-receptors, and the stereoisomer (−)-baclofen, a full agonist, also prevented the effect of dopamine on the veratridine-induced release of CCK-LI. The effects of both drugs may be due to desensitization of GABAB-receptors, which has been described to develop quite rapidly. It is concluded that δ-amino-n-valeric acid blocks GABAB-receptors and in this way prevents the enhancement of the veratridine-induced release of CCK-LI caused by dopamine via D2-receptors. These data are interpreted as evidence that dopamine and GABA-neurons can directly or indirectly interact in the rat neostriatum.