Intrastriatal dopamine D1 antagonism dampens neural plasticity in response to motor cortex lesion

Abstract

Motor cortex lesions in rats partially denervate the striatum, producing behavioral deficits and inducing reactive neuroplasticity. Plastic responses include changes in growth-associated protein marker expression and anatomical restructuring. Corticostriatal plasticity is dependent on dopamine at the striatal target, where D1 receptor signaling reinforces behaviorally relevant neural activity. To determine whether striatal dopamine D1 receptor signaling is important for the growth-associated protein responses and behavioral recovery that follow unilateral motor cortex aspiration, the dopamine D1 receptor antagonist SCH23390 was intrastriatally infused in cortically lesioned animals. After a cortical aspiration lesion in Long Evans rats, the growth-associated proteins SCG10 and GAP-43 were upregulated in the cortex contralateral to the lesion at 30 days post-lesion. However, continuous unilateral intrastriatal infusion of SCH23390 prevented this aspiration-induced upregulation. Furthermore, lesioned rats demonstrated spontaneous sensorimotor improvement, in terms of limb-use symmetry, about one month post-lesion. This improvement was prevented with chronic intrastriatal SCH23390 infusion. The D1 receptor influence may be important to normalize corticostriatal activity (and observable behavior), either in a long-term manner or temporarily until other more permanent means of synaptic regulation, such as sprouting or synaptogenesis, may be implemented. Keywords cortical ablation; striatum; SCH23390The ability to reorganize neural connections according to changing environmental cues is essential to the formation of the wide network of limbic, striatal, and cortical circuits that regulate the complex array of human behaviors. Generally referred to as neural plasticity, these adaptive processes are most obvious in the developing brain, but are also utilized throughout adulthood as new skills and memories are acquired. Likewise, when the brain is damaged by trauma or disease, adaptive mechanisms of plasticity are brought into play and are critical for determining the limits of functional recovery (Ivanco and Greenough, 2000,Johansson, 2000,Nudo et al., 2001,Gonzalez and Kolb, 2003. These adaptive processes are governed by local extra-and intracellular signals and can be manipulated by various experimental interventions including: exercise (Cotman and Berchtold, 2002,Gomez-Pinilla et al., 2002) Tel: 323-442-2126; Fax: 323-442-2127. E-mail address: elizabjd@usc.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (van Praag et al., 2000), motor skills training (Plautz et a...

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