Elucidating the role of 5-HT_1A and 5-HT₇ receptors on 8-OH-DPAT-induced behavioral recovery after experimental traumatic brain injury

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• 作者：Narayana K. Yelleswarapu^a ; ^b ; Justin K. Tay^a ; ^b ; William M. Fryer^a ; ^b ; Mansi A. Shah^a ; ^b ; ^c ; Alexandra N. Garcia^a ; ^b ; ¹ ; Jeffrey P. Cheng^a ; ^b ; Anthony E. Kline^a ; ^b ; ^c ; ^d ; ^e ; ^{klineae@upmc.edu}
• 关键词：5-HT ; serotonin ; 8-OH-DPAT ; 8-hydroxy-2-(di-n-propylamino)tetralin ; WAY 100635 ; N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamide ; SB 269970 HCl ; (2R)-1-[(3-Hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl] py
• 刊名：Neuroscience Letters
• 出版年：2012
• 期刊代码：52_03043940
• 类别：neu
• 出版时间：2 May, 2012
• 卷：515
• 期：2
• 页码：153-156
• 文件大小：329 K

摘要

8-OH-DPAT is a 5-HT_1A/7 receptor agonist that enhances behavioral recovery after traumatic brain injury (TBI). This study is a first attempt to decipher whether the benefits induced by 8-OH-DPAT after TBI are mediated by 5-HT_1A or 5-HT₇ receptors. A single i.p. injection of 8-OH-DPAT (0.5 mg/kg) alone or co-administered with either the 5-HT_1A or 5-HT₇ receptor antagonists WAY 100635 (0.5 mg/kg) or SB 269970 HCl (2.0 mg/kg), respectively, or vehicle control (1.0 mL/kg) was given 15 min after cortical impact or sham injury. Function was assessed by established motor and cognitive tests. No difference in motor performance was observed among the TBI groups. Spatial acquisition was enhanced, relative to vehicle controls, by 8-OH-DPAT alone and when co-administered with WAY 100635, but not when combined with SB 269970 HCl. These data imply that 5-HT_1A receptor antagonism does not abate the 8-OH-DPAT-induced cognitive benefits, but 5-HT₇ receptor antagonism does, which suggests that the 8-OH-DPAT-induced benefits in this single administration paradigm may be mediated more by 5-HT₇ versus 5-HT_1A receptors. Evaluation of a specific 5-HT₇ receptor agonist will further elucidate the contribution of 5-HT_1A and 5-HT₇ receptors on behavioral recovery conferred by acute 8-OH-DPAT treatment after TBI.