Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity

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 D-1 receptors have been used to investigate the involvement of the D-1-like class (D-1 and D-5) of DA receptors in locomotion and corticostriatal long-term depression (LTD) and long-term potentiation (LTP). Our results suggest that D-1 and D-5 receptors exert distinct actions on both activity-dependent synaptic plasticity and spontaneous motor activity. Accordingly, the ablation of D-1 receptors disrupted corticostriatal LTP, whereas pharmacological blockade of D-5 receptors prevented LTD. On the other side, genetic ablation of D-1 receptors increased locomotor activity, whereas the D-1/D-5 receptor antagonist SCH 23390 decreased motor activity in both control mice and mice lacking D-1 receptors. Endogenous DA stimulated D-1 and D-5 receptors in distinct subtypes of striatal neurons to induce, respectively, LTP and LTD. In control mice, in fact, LTP was blocked by inhibiting the D-1-protein kinase A pathway in the recorded spiny neuron, whereas the striatal nitric oxide-producing interneuron was presumably the neuronal subtype stimulated by D-5 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.