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

Publisher Website
Google Scholar
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 D1receptors have been used to investigate the involvement of the D1-like class (D1and D5) of DA receptors in locomotion and corticostriatal long-term depression (LTD) and long-term potentiation (LTP). Our results suggest that D1and D5receptors exert distinct actions on both activity-dependent synaptic plasticity and spontaneous motor activity. Accordingly, the ablation of D1receptors disrupted corticostriatal LTP, whereas pharmacological blockade of D5receptors prevented LTD. On the other side, genetic ablation of D1receptors increased locomotor activity, whereas the D1/D5receptor antagonist SCH 23390 decreased motor activity in both control mice and mice lacking D1receptors.Endogenous DA stimulated D1and D5receptors 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 D5receptors 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.