Elucidating the role of 5-HT(1A) and 5-HT(7) receptors on 8-OH-DPAT-induced behavioral recovery after experimental traumatic brain injury.

Abstract:

: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-HT(7) 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-HT(7) 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-HT(7) receptor antagonism does, which suggests that the 8-OH-DPAT-induced benefits in this single administration paradigm may be mediated more by 5-HT(7) versus 5-HT(1A) receptors. Evaluation of a specific 5-HT(7) receptor agonist will further elucidate the contribution of 5-HT(1A) and 5-HT(7) receptors on behavioral recovery conferred by acute 8-OH-DPAT treatment after TBI.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Yelleswarapu NK,Tay JK,Fryer WM,Shah MA,Garcia AN,Cheng JP,Kline AE

doi

10.1016/j.neulet.2012.03.033

subject

Has Abstract

pub_date

2012-05-02 00:00:00

pages

153-6

issue

2

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(12)00403-X

journal_volume

515

pub_type

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