D2R striatopallidal neurons inhibit both locomotor and drug reward processes

• Published in: Nature neuroscience Vol. 12; no. 4; pp. 393 - 395
• Main Authors: Durieux, Pierre F, Bearzatto, Bertrand, Guiducci, Stefania, Buch, Thorsten, Waisman, Ari, Zoli, Michele, Schiffmann, Serge N, de Kerchove d'Exaerde, Alban
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2009; Nature Publishing Group
• Subjects: Amphetamine - pharmacology; Animal Genetics and Genomics; Animals; Autoradiography; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; brief-communication; Conditioning, Operant - physiology; Corpus Striatum - cytology; Diphtheria Toxin - pharmacology; Dopamine Uptake Inhibitors - pharmacology; Enkephalins - genetics; Enkephalins - metabolism; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Globus Pallidus - cytology; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - metabolism; Heparin-binding EGF-like Growth Factor; Intercellular Signaling Peptides and Proteins - genetics; Locomotion - drug effects; Locomotion - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins - metabolism; Neurobiology; Neurons - drug effects; Neurons - physiology; Neurosciences; Protein Binding - drug effects; Receptors, Adenosine A2 - genetics; Receptors, Dopamine D2 - deficiency; Receptors, Dopamine D2 - metabolism; Reinforcement Schedule; Reward; Time Factors; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.2286

The striatum contains two distinct types of GABAergic neurons, striatonigral and striatopallidal cells. Durieux and colleagues genetically ablated the striatopallidal population in mice, uncovering specific roles for these neurons in the control of locomotion and the response to the addictive drug amphetamine. The specific functions of dopamine D 2 receptor–positive (D 2 R) striatopallidal neurons remain poorly understood. Using a genetic mouse model, we found that ablation of D 2 R neurons in the entire striatum induced hyperlocomotion, whereas ablation in the ventral striatum increased amphetamine conditioned place preference. Thus D 2 R striatopallidal neurons limit both locomotion and, unexpectedly, drug reinforcement.