کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4332268 1292892 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of the 5-HT2C receptor in improving weight-supported stepping in adult rats spinalized as neonates
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Role of the 5-HT2C receptor in improving weight-supported stepping in adult rats spinalized as neonates
چکیده انگلیسی

Loss of descending serotonergic (5-HT) projections after spinal cord injury (SCI) contributes to motor deficits and upregulation of receptors on partially denervated serotonergic targets in the spinal cord. Serotonergic agonists acting on these upregulated receptors are potential therapeutic agents that could ameliorate motor deficits. However, modification of 5-HT receptors following complete spinal cord injury results in different effects by 5-HT2C receptor agonists and antagonists. For example, administration of 5-HT2C receptor agonists suppresses locomotor activity in normal animals, but enhances it in spinalized animals. In addition, administration of 5-HT2C receptor agonists does not induce activity-dependent hindlimb tremors in normal animals, but does induce them in spinalized animals. We therefore extended our previous work with the 5-HT2C receptor agonist 1-(m-chlorophenyl)-piperazine hydrochloride (mCPP), which enhances weight-supported stepping when administered to adult rats spinalized as neonates, to identify the optimal dose for improved weight-supported stepping with minimal side effects. In order to determine whether mCPP enhances weight-supported stepping after SCI is through activation of the 5-HT2C receptor, we performed the following experiments. We determined that stimulation of the 5-HT1A receptor did not contribute to this improvement in weight-support. We reversed the increase in mCPP-induced weight-supported stepping with SB 206,553, a 5-HT2C receptor antagonist. We also provide evidence for denervation-induced upregulation of 5-HT2C receptors in the injured spinal cord. Since mCPP does not have the behavioral toxicity associated with non-selective 5-HT2 receptor agonists, targeting the 5-HT2C receptor may have clinical relevance for the treatment of SCI.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1112, Issue 1, 27 September 2006, Pages 159–168
نویسندگان
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