Local application of SCH 39166 reversibly and dose-dependently decreases acetylcholine release in the rat striatum

The effect of local application by reverse dialysis of the dopamine D-1 receptor antagonist (-)-trans-6,7,7a,8,9,13 b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-naphto-[2,1b]-azepine hydrochloride (SCH 39166) on acetylcholine release was studied in awake, freely moving rats implanted with concentric microdialysis probes in the dorsal striatum. In these experiments, the reversible acetylcholine esterase inhibitor, neostigmine, was added to the perfusion solution at two different concentrations, 0.01 and 0.1 mu M. SCH 39166 (1, 5 and 10 mu M), in the presence of 0.01 mu M neostigmine, reversibly decreased striatal acetylcholine release (1 mu M SCH 39166 by 8 +/- 4%; 5 mu M SCH 39166 by 24 +/- 5%; 10 mu M SCH 39166 by 27 +/- 7%, from basal). Similarly, SCH 39166, applied in the presence of a higher neostigmine concentration (0.1 mu M), decreased striatal acetylcholine release by 14 +/- 4% at 1 mu M, by 28 +/- 8% at 5 mu M and by 30 +/- 5% at 10 mu M, in a dose-dependent and time-dependent manner. These results are consistent with the existence of a facilitatory tone of dopamine on striatal acetylcholine transmission mediated by dopamine D-1 receptors located on striatal cholinergic interneurons. (C) 1999 Elsevier Science B.V. All rights reserved.