Elucidating the role of 5-HT1A and 5-HT7 receptors on 8-OH-DPAT-induced behavioral recovery after experimental traumatic brain injury

8-OH-DPAT is a 5-HT1A/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-HT1A 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-HT1A or 5-HT7 receptor antagonists WAY 100635 (0.5 mg/kg) or SB 269970 HCI (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 HCI. These data imply that 5-HT1A receptor antagonism does not abate the 8-OH-DPAT-induced cognitive benefits, but 5-HT7 recepi:or 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-HT1A receptors. Evaluation of a specific 5-HT7 receptor agonist will further elucidate the contribution of 5-HTIA and 5-HT7 receptors on behavioral recovery conferred by acute 8-OH-DPAT treatment after TBI. (C) 2012 Elsevier Ireland Ltd. All rights reserved.