In Vivo Striatal Dopamine Release by M1 Muscarinic Receptors Is Induced by Activation of Protein Kinase C

Abstract

Islet-activating protein was unilaterally microinjected into rat striatum, and a dialysis cannula was implanted into the same area under anesthesia. After 2 days, various agents were perfused continuously into the striatum through the dialysis membrane, under freely moving conditions. Islet-activating protein (2 .mu.g/2 .mu.l) treatment alone did not change in vivo striatal dopamine (DA) release and metabolism, but completely abolished the increase of striatal DA release evoked in vivo by the M1-selective agonist McN-A-343 (10-7 M). Forskolin (10-5 M), an adenylate cyclase activator, increased DA release and showed an additive effect on the DA release evoked by McN-A-343. Polymyxin B, a rather selective inhibitor of protein kinase C, decreased DA release and completely blocked the effect of McN-A-343. These results suggest that in vivo striatal DA release elicited by M1 muscarinic receptors is coupled with interaction with a Go protein and is induced by activation of protein kinase C.