Role of dopamine D-1 receptors in the control of striatal acetylcholine release by endogenous dopamine

In order to determine the role of dopamine (DA) DI receptors in the control of striatal acetylcholine (ACh) transmission, we studied the effects of SCH 39166 (D-1 receptor antagonist), alone or in combination with quinpirole (D-2/D-3 agonist) or PD 128,907 (D-3 agonist) on ACh and DA release. Quinpirole reduced DA and ACh release; PD 128,907 decreased DA but not ACh release. SCH 39166 stimulated DA and decreased ACh release. Pretreatment with quinpirole reduced or prevented (depending on the dose) the stimulation of DA release while potentiating the decrease of ACh release elicited by SCH 39166. Similarly, SCH 39166 administered following PD 128,907 did not stimulate DA release, further decreasing ACh release. These results indicate that quinpirole or PD 128,907 affect the actions of SCH 39166 on DA and ACh release in opposite manner, counteracting the increase of DA release and potentiating the reduction of ACh release. These data support the tenet that endogenous DA exerts a stimulatory input on striatal ACh neurotransmission mediated by D-1 receptors.