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The Journal of Neuroscience, September 17, 2003, 23(24):8506-8512
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Distinct Roles of D1 and D5 Dopamine Receptors in Motor Activity and Striatal Synaptic Plasticity
Diego Centonze,1,2 Cristina Grande,3 Emilia Saulle,1,2 Ana B. Martín,3 Paolo Gubellini,1,2,4 Nancy Pavón,3 Antonio Pisani,1,2 Giorgio Bernardi,1,2 Rosario Moratalla,3 * andPaolo Calabresi1,2 * 1Clinica Neurologica, Dipartimento di Neuroscienze, Università di Tor Vergata, 00133 Rome, Italy, 2Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Santa Lucia, 00179 Rome, Italy, 3Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain, and 4Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, Centre National de la Recherche Scientifique, 13402 Marseille Cedex 20, France
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.
Key words: basal ganglia; behavior; in vitro electrophysiology; interneurons; long-term depression; long-term potentiation; nitric oxide
Received March 20, 2003; revised June 24, 2003; accepted July 17, 2003.
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