Distinct Roles of D₁and D₅Dopamine Receptors in Motor Activity and Striatal Synaptic Plasticity

Abstract

Stimulation of dopamine (DA) receptors in the striatum is essential for voluntary motor activity and for the generation of plasticity at corticostriatal synapses. In the present study, mice lacking DA D1 receptors have been used to investigate the involvement of the D1-like class (D1 and D5) of DA receptors in locomotion and corticostriatal long-term depression (LTD) and long-term potentiation (LTP). Our results suggest that D1 and D5 receptors exert distinct actions on both activity-dependent synaptic plasticity and spontaneous motor activity. Accordingly, the ablation of D1 receptors disrupted corticostriatal LTP, whereas pharmacological blockade of D5 receptors prevented LTD. On the other side, genetic ablation of D1 receptors increased locomotor activity, whereas the D1/D5 receptor antagonist SCH 23390 decreased motor activity in both control mice and mice lacking D1 receptors. Endogenous DA stimulated D1 and D5 receptors in distinct subtypes of striatal neurons to induce, respectively, LTP and LTD. In control mice, in fact, LTP was blocked by inhibiting the D1-protein kinase A pathway in the recorded spiny neuron, whereas the striatal nitric oxide-producing interneuron was presumably the neuronal subtype stimulated by D5 receptors during the induction phase of LTD. Understanding the role of DA receptors in striatal function is essential to gain insights into the neural bases of critical brain functions and of dramatic pathological conditions such as Parkinson's disease, schizophrenia, and drug addiction.

Differential Contributions of Dopamine D1, D2, and D3 Receptors to MDMA-Induced Effects on Locomotor Behavior Patterns in Mice

“…These data contrast with reports in rats that the D 1 /D 5 receptor antagonist SCH23390 reduced MDMA-induced hyperactivity (Ball et al, 2003;Bubar et al, 2004). SCH23390, however, also reduces locomotor activity in D 1 KO mice, indicating that the locomotor-reducing effects of SCH23390 may not be due solely to D 1 receptor blockade (Centonze et al, 2003). SCH23390 is an antagonist at both D 1 and D 5 receptors (Lawler et al, 1999), as well as 5-HT 2C receptors (Millan et al, 2001).…”

Computational models of reinforcement learning: the role of dopamine as a reward signal

“…Synaptic plasticity has indeed been shown to occur at target structures of the VTA, including the NAc (Kombian and Malenka 1994;Li and Kauer 2004;Pennartz et al 1993;Robbe et al 2002;Taverna and Pennartz 2003;Thomas et al 2001), PFC (Otani et al 2003) and amygdala (Bauer and LeDoux 2004;Bauer et al 2002;Fourcaudot et al 2009;Kandel 1998, 2007;Humeau et al 2003;Samson and Pare 2005). DA was shown to modulate plasticity in the striatum (Calabresi et al 2007;Centonze et al 2003;Kerr and Wickens 2001;Pawlak and Kerr 2008;Reynolds et al 2001), the amygdala (Bissière et al 2003), PFC Kolomiets et al 2009) and hippocampus (Frey et al 1989(Frey et al , 1990(Frey et al , 1991Lisman 1996, 1998;Gurden et al 1999) but not in the NAc. Behaviorally, it was also shown that pharmacological manipulations of DA levels in the brain shortly after performance can alter memory consolidation or reconsolidation (Dalley et al 2005;Fenu and Fig.…”

Motor-Skill Learning-Associated Gene Regulation in the Striatum: Effects of Cocaine

“…Both LTP and LTD are dependent on dopamine input (Calabresi et al, 1996;Centonze et al, 2001;Reynolds and Wickens, 2002), with low dopamine levels apparently favoring LTD and high dopamine levels producing LTP at the corticostriatal synapse (Reynolds and Wickens, 2002). Notably, such LTP is blocked by D1 receptor antagonism (Kerr and Wickens, 2001;Reynolds et al, 2001;Centonze et al, 2003).…”