8-OH-DPAT (8-Hydroxy-DPAT)

8-OH-DPAT, at a pIC50 of 8.19, exhibits robust and specific agonistic activity on 5-HT1A receptors, indicating high selectivity. However, 8-OH-DPAT shows only weak binding affinity towards 5-HT1B receptors (pIC50, 5.42) and minimal binding to 5-HT receptors (pIC50

Pretreatment of 8-OH-DPAT over the concentration range of 1-100µM significantly inhibited the H2O2 -induced neuronal cell death[3].8-OH-DPAT(10 µM;24 h) reduces lipofuscin accumulation in cultured RPE cells[4].

In rats administered with 8-OH-DPAT(0-0.1 mg/kg; s.c.;2h) and provided with wet mash, feeding and activity frequencies were increased, while resting and total grooming behaviors were inhibited in non-deprived conditions[5]. 8-OH-DPAT(0.5 mg/kg；s.c) enhanced QUIN' (an agonist quinpirole) and HAL's(a potent D₂ antagonist haloperidol) disruption of pup retrieval and pup preference, reversed the increase in hovering over pups induced by HAL in mice[6]. 8-OH-DPAT(0.2 and 0.4mg/kg i.p.) reduces competition from contextual but not discrete conditioning cues[7]. Systemically injected 8-OH-DPAT (0.4 mg/kg) decreased extracellular 5-HT levels in the medial preoptic area (MPOA) as measured by in vivo microdialysis[8].

References:
[1]. Middlemiss DN, Fozard JR. 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol. 1983 May 20;90(1):151-3. doi: 10.1016/0014-2999(83)90230-3. PMID: 6223827.
[2]. Bard JA, Zgombick J, et,al. Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem. 1993 Nov 5;268(31):23422-6. PMID: 8226867.
[3]. Lee HJ, Ban JY, et,al. Stimulation of 5-HT1A receptor with 8-OH-DPAT inhibits hydrogen peroxide-induced neurotoxicity in cultured rat cortical cells. Pharmacol Res. 2005 Mar;51(3):261-8. doi: 10.1016/j.phrs.2004.09.003. PMID: 15661577.
[4]. Thampi P, Rao HV, et,al. The 5HT1a receptor agonist 8-Oh DPAT induces protection from lipofuscin accumulation and oxidative stress in the retinal pigment epithelium. PLoS One. 2012;7(4):e34468. doi: 10.1371/journal.pone.0034468. Epub 2012 Apr 3. PMID: 22509307; PMCID: PMC3317995.
[5]. Hartley JE, Montgomery AM. 8-OH-DPAT inhibits both prandial and waterspray-induced grooming. J Psychopharmacol. 2008 Sep;22(7):746-52. doi: 10.1177/0269881107082903. Epub 2008 Feb 28. PMID: 18308782.
[6]. Cai Y, Zhang X, et,al. 8-OH-DPAT enhances dopamine D2-induced maternal disruption in rats. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2022 Jul;208(4):467-477. doi: 10.1007/s00359-022-01551-4. Epub 2022 Apr 17. PMID: 35434766.
[7]. Cassaday HJ, Thur KE. Intraperitoneal 8-OH-DPAT reduces competition from contextual but not discrete conditioning cues. Pharmacol Biochem Behav. 2019 Dec;187:172797. doi: 10.1016/j.pbb.2019.172797. Epub 2019 Oct 24. PMID: 31669833; PMCID: PMC6899499.
[8]. Lorrain DS, Matuszewich L, et,al. 8-OH-DPAT influences extracellular levels of serotonin and dopamine in the medial preoptic area of male rats. Brain Res. 1998 Apr 20;790(1-2):217-23. doi: 10.1016/s0006-8993(98)00065-1. PMID: 9593901.

8-OH-DPAT 是5-HT1A 激动剂, pIC50 值为 8.19 ,此外8-OH-DPAT对5-HT1B(pIC50 , 5.42)和5-HT (pIC50 <5)受体亲和力都很弱 [1-2]。
8-OH-DPAT预处理(1 ~ 100μM)可显著抑制H2O2诱导的神经细胞死亡[3]。8-OH-DPAT(10 μM;24 h)可减少培养的RPE细胞中脂褐素的积累[4]。
在给予8-OH-DPAT(0-0.1 mg/kg; s.c.;2h)并提供湿糊状食物的大鼠中,饮食和活动频率增加,而休息和总梳洗行为在非剥夺条件下被抑制[5]。8-OH-DPAT（0.5 mg/kg；s.c）增强了喹啉和苯环丙胺（HAL）对大鼠拾取幼崽和对幼崽的优先性的干扰作用,并在小鼠中逆转了HAL引起的对幼崽的悬停增加[6]。8-OH-DPAT（0.2和0.4 mg/kg；i.p）减少了来自情境条件但不是离散条件线索的竞争[7]。8-OH-DPAT（0.4 mg/kg）可降低内侧视前区(MPOA)细胞外5-HT水平[8]。