title: Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum.
abstract: Evidence indicates that dopamine receptors regulate processes of procedural learning in the sensorimotor striatum. Our previous studies revealed that the indirect dopamine receptor agonist cocaine alters motor-skill learning-associated gene regulation in the sensorimotor striatum. Cocaine-induced gene regulation in the striatum is principally mediated by D1 dopamine receptors. We investigated the effects of cocaine and striatal D1 receptor antagonism on motor-skill learning. Rats were trained on a running wheel (40-60 min, 2-5 days) to learn a new motor skill, that is, the ability to control the movement of the wheel. Immediately before each training session, the animals received an injection of vehicle or cocaine (25 mg/kg, i.p.), and/or the D1 receptor antagonist SCH-23390 (0, 3, 10 microg/kg, i.p., or 0, 0.3, 1 microg, intrastriatal via chronically implanted cannula). The animal's ability to control/balance the moving wheel (wheel skill) was tested before and repeatedly after the training. Normal wheel-skill memory lasted for at least 4 weeks. Cocaine administered before the training tended to attenuate skill learning. Systemic administration of SCH-23390 alone also impaired skill learning. However, cocaine given in conjunction with the lower SCH-23390 dose (3 microg/kg) reversed the inhibition of skill learning produced by the D1 receptor antagonist, enabling intact skill performance during the whole post-training period. In contrast, when cocaine was administered with the higher SCH-23390 dose (10 microg/kg), skill performance was normalized 1-6 days after the training, but these rats lost their improved wheel skill by day 18 after the training. Similar effects were produced by SCH-23390 (0.3-1 microg) infused into the striatum. Our results indicate that cocaine interferes with normal motor-skill learning, which seems to be dependent on optimal D1 receptor signaling. Furthermore, our findings demonstrate that D1 receptors in the striatum are critical for consolidation of long-term skill memory.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
authors.forename: I
authors.initials: I
authors.lastname: Willuhn
authors.forename: H
authors.initials: H
authors.lastname: Steiner
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D003042:Cocaine