THE POTENT AND SELECTIVE DOPAMINE D-1 RECEPTOR AGONIST A-77636 INCREASES CORTICAL AND HIPPOCAMPAL ACETYLCHOLINE-RELEASE IN THE RAT

The effects of systemic administration of the full dopamine D-1 receptor agonist A-77636 on acetylcholine release in rat frontal cortex and hippocampus were studied using in vivo microdialysis. Administration of A-77636 (4 mu mol/kg s.c.) greatly (> 230%) increased both cortical and hippocampal acetylcholine release for more than 3 h; at a lower dose (1 mu mol/kg s.c.) A-77636 significantly stimulated cortical but not hippocampal acetylcholine release. The effect of the;higher dose of A-77636 on cortical acetylcholine release was blocked by the dopamine D-1 receptor antagonist SCH 23390 (300 mu g/kg s.c.). These results confirm that stimulation of dopamine D-1 receptors facilitates cortical and hippocampal acetylcholine release in vivo, and indicate that these two structures are differentially sensitive to this effect. They also raise the possibility that dopamine D-1 receptor agonists may be useful in the treatment of cortical and hippocampal acetylcholine deficit-related syndromes.