Co-dergocrine (Hydergine) regulates striatal and hippocampal acetylcholine release through D2 receptors.

The effect of Co-dergocrine (Hydergine) on acetylcholine (ACh) release in the striatum and hippocampus has been studied by means of brain microdialysis and compared to the effect of SKF 38393 and of LY 171555 selective D1 and D2 dopamine (DA) receptor agonists, respectively. Co-dergocrine (1 and 5 mg kg-1 i.p.) as well as LY 171555 (0.2 and 0.5 mg kg-1 i.p.) decreased the extracellular concentration of ACh in the striatum, whereas SKF 38393 (5 and 10 mg kg-1 i.p.) increased it. On the other hand, Co-dergocrine (1 and 5 mg kg-1), LY 171555 (0.2 and 0.5 mg kg-1) and SKF 38393 (5 and 10 mg kg-1) increased ACh release in the hippocampus in a dose-dependent way. These results show that Co-dergocrine, which is widely used in the treatment of senile mental decline, enhances the release of ACh in the hippocampus in a similar manner to both D1 and D2 DA agonists. This effect might be relevant for the amelioration of cognitive processes. Moreover, our results which demonstrate that Co-dergocrine is able to decrease the release of ACh in the striatum, as are selective D2 agonists, suggest that Co-dergocrine may have a potential therapeutic benefit in Parkinsonian dementia.