Willuhn I, Steiner H. Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum. Neuroscience 153: 249-258

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.
Neuroscience (Impact Factor: 3.36). 05/2008; 153(1):249-58. DOI: 10.1016/j.neuroscience.2008.01.041
Source: PubMed


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.

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    • "Cocaine modulates the action of D1 dopamine receptors, associated with c-fos gene regulation in the striatum (Graybiel et al., 1990; Gerfen et al., 1995). Therefore, it has been suggested that cocaine encodes the transcription of motor skill learning (Willuhn and Steiner, 2008). Dopamine dysfunction or deficiency in the striatum is the major clinical observation in Parkinsonism (Khan et al., 2002). "
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    ABSTRACT: The motor cortex and dorsal striatum (caudate nucleus and putamen) are key regions in motor processing but the interface between the cortex and striatum is not well understood. While dorsal striatum integrates information from multiple brain regions to shape motor learning and habit formation, the disruption of cortico-striatal circuits compromises the functionality of these circuits resulting in a multitude of neurologic disorders, including Parkinson's disease. To better understand the modulation of the cortico-striatal circuits we recorded simultaneously single neuron activity from four brain regions, primary motor, and sensory cortices, together with the rostral and caudal segments of the putamen in rhesus monkeys performing a visual motor task. Results show that spatial and temporal-task related firing relationships between these cortico-striatal circuit regions were modified by the independent administration of the two drugs (cocaine and baclofen). Spatial tuning and correlated firing of neurons from motor cortex and putamen were severely disrupted by cocaine and baclofen on correct trials, while the two drugs have dramatically decreased the functional connectivity of the motor cortical-striatal network. These findings provide insight into the modulation of cortical-striatal firing related to movement with implications for therapeutic approaches to Parkinson's disease and related disorders.
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    • "Recent findings have suggested that the generation of aberrant procedural memories in striatal motor circuits could participate in the manifestation of abnormal motor responses associated with DRT (Calon et al., 2000; Pisani et al., 2005; Jenner, 2008; Simola et al., 2009; Frau et al., 2013). Thus, the striatum plays a major role in processes such as integration of motor signals, acquisition of motor habits, and execution of motor programs, which are all critically regulated by dopamine (Mink, 1996; Packard and Knowlton, 2002; Gerdeman et al., 2003; Tang et al., 2007; Willuhn and Steiner, 2008). Starting from these premises, it has been hypothesized that the dopamine-denervated striatum fails to properly process motor information, and that this may result in an overload of striatal motor circuits following the performance of movement stimulated by drugs that activate dopamine receptors (Picconi et al., 2005; Pisani et al., 2005). "
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    • "Dopaminergic signals in the striatum and motor cortex play essential roles in the induction of synaptic plasticity and motor skill acquisition. Administration of a D1 receptor antagonist to the striatum previously resulted in impaired motor skill acquisition [12] [13], while 11C-raclopride positron emission tomography (PET) showed dopamine release in the striatum during new motor sequence learning [14]. The motor cortex is also associated with encoding elementary aspects of movement such as dynamic acceleration and force [15], [16], [17]. "
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