Stimulation of both dopamine D1 and D2 receptors facilitates in vivo acetylcholine release in the hippocampus.

The effect of selective D1 and D2 dopamine (DA) receptor agonists and of a mixed D1/D2 agonist on hippocampal acetylcholine (ACh) release was investigated. LY 171555 (0.5 and 1 mg/kg, i.p.), SKF 38393 (1 to 10 mg/kg, i.p.), CY 208-243 (0.2 mg/kg, i.p.) and apomorphine (0.5 to 2 mg/kg, i.p.), at doses stimulating rat behavior, were found to increase the output of ACh in the hippocampus. Maximal increase was observed after LY 171555 1 mg/kg, SKF 38393 10 mg/kg, CY 208-243 2 mg/kg and apomorphine 2 mg/kg (85, 90, 87 and 210%, respectively). The enhancement of ACh release induced by either SKF 38393 (10 mg/kg) or LY 171555 (1 mg/kg) was prevented by the blockade of D1 receptors with SCH 23390 (0.1 mg/kg, s.c.). Co-administration of maximally active doses of LY 171555 (1 mg/kg) and SKF 38393 (10 mg/kg) produced an additive effect (about 200%). In contrast to the findings with high doses, low, presynaptic doses of LY 171555 and apomorphine reduced ACh output. Maximal reduction was observed after 0.05 mg/kg for both drugs, (43 and 52%, respectively). These results show that activation of dopaminergic transmission either at D1 and/or at D2 receptors enhances ACh output in the hippocampus.