Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats.

Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats.
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DOI:
10.1007/s00213-008-1136-5
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发表时间:
2008-07
期刊:
影响因子:
3.4
通讯作者:
Bartlett, Selena E.
Bartlett, Selena E.
中科院分区:
医学3区
文献类型:
--
作者:
Richards, Jemma K.;Simms, Jeffrey A.;Steensland, Pia;Taha, Sharif A.;Borgland, Stephanie L.;Bonci, Antonello;Bartlett, Selena E.

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先前的研究表明,食欲素-1/下丘脑泌素-1受体在自我给药和线索诱导的食物、药物和乙醇寻求的恢复中发挥作用。在目前的研究中,我们研究了食欲素-1/下丘脑泌素-1受体在乙醇和蔗糖的操作性自我管理和育亨宾诱导的乙醇和蔗糖寻求恢复中的作用。训练大鼠自我给予10%乙醇或5%蔗糖(30分钟/天)。食欲素-1受体拮抗剂SB 334867(0、5、10、15、20 mg/kg,i. p.)在操作性自我给药前30 min给药。在这些实验之后,乙醇和蔗糖训练的大鼠的操作性自我给药行为都消失了。在达到消退标准后,将SB 334867(0、5、10 mg/kg,i. p.)在育亨宾(0或2 mg/kg,i. p.)前30分钟给药。在单独的实验中,SB 334867(0、15或20 mg/kg,i. p.)使用旷场试验测定对一般运动活动的影响。食欲素-1受体拮抗剂SB 334867(10,15和20 mg/kg)减少了10%乙醇的操作性自我给药,但不减少5%蔗糖的自我给药。此外,SB 334867(5和10 mg/kg)显着降低育亨宾诱导的恢复乙醇和蔗糖寻求。SB 334867没有显著影响使用旷场试验测量的自发活动。结果表明,OX-1/Hcrt-1受体的抑制调节操作性乙醇自我管理,并在育亨宾诱导的恢复乙醇和蔗糖寻求在大鼠中也起着重要的作用。
Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.
DOI: 10.1016/j.neuroscience.2005.10.062
发表时间: 2006-01-01
期刊: NEUROSCIENCE
影响因子: 3.3
作者:
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通讯作者: Lê, AD
DOI: 10.1016/j.neuron.2006.01.016
发表时间: 2006-02-16
期刊: NEURON
影响因子: 16.2
作者:
Borgland, SL;Taha, SA;Bonci, A
通讯作者: Bonci, A
DOI: 10.1073/pnas.0507480102
发表时间: 2005-12-27
影响因子: 11.1
作者:
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通讯作者: de Lecea, L
DOI: 10.1007/s002130050150
发表时间: 1996-12-01
期刊: PSYCHOPHARMACOLOGY
影响因子: 3.4
作者:
Erb, S;Shaham, Y;Stewart, J
通讯作者: Stewart, J
DOI: 10.1038/nature04071
发表时间: 2005-09-22
期刊: NATURE
影响因子: 64.8
作者:
Harris, GC;Wimmer, M;Aston-Jones, G
通讯作者: Aston-Jones, G