Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3,4-DCPG
Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3,4-DCPG
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DOI：
10.1016/j.ejphar.2005.10.051
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发表时间：
2005-12-28
影响因子：
5
通讯作者：
Hyytiä, P
中科院分区：
文献类型：
--
作者：
Bäckström, P;Hyytiä, P
谷氨酸能神经传递被认为调节线索诱导的药物寻求行为。在这里，我们研究了代谢型谷氨酸受体激动剂对酒精自我管理和线索诱导的恢复的影响。训练大鼠在30分钟的会议期间根据FR 1强化时间表自我施用10%w/v乙醇。在恢复实验中，乙醇和非奖励奎宁溶液（可在交替的日子）与嗅觉刺激（S+/S-）以及光（CS+）或音（CS-）刺激配对。消退训练后，乙醇相关刺激（S+/CS+）诱导反应恢复。将mGlu 2/3受体激动剂LY 379268（0、1、3和5 mg/kg i. p.）和mGlu 8受体激动剂（S）-3，4-DCPG（0、5、10和15 mg/ka i. p.）减弱酒精自我给药，并在降低自发运动活动的剂量下恢复。结果表明，代谢型谷氨酸受体可能在酒精寻求和自我管理的调制中发挥作用。然而，需要进一步研究具有较少运动抑制剂副作用的配体。(c)2005 Elsevier B. V.保留所有权利。
Glutamatergic neurotransmission has been suggested to modulate cue-induced drug-seeking behavior. Here we examined the effects of metabotropic glutamate receptor agonists on alcohol self-administration and cue-induced reinstatement. Rats were trained to self-administer 10% w/v ethanol under an FR1 schedule of reinforcement during 30-min sessions. In the reinstatement experiments, ethanol and a non-rewarding quinine solution (available on alternating days) were paired with olfactory stimuli (S+/S-) as well as light (CS+) or tone (CS-) stimuli. Following extinction training, reinstatement of responding was induced by the ethanol-associated stimuli (S+/CS+). The mGlu2/3 receptor agonist LY379268 (0, 1, 3 and 5 mg/kg i.p.) and the mGlu8 receptor agonist (S)-3,4-DCPG (0, 5, 10 and 15 mg/ka i.p.) attenuated alcohol self-administration and reinstatement at doses that decreased also spontaneous locomotor activity. The results suggest that metabotropic glutamate receptors may have a role in the modulation of alcohol seeking and self-administration. However, further studies with ligands with fewer motor-suppressant side effects are needed. (c) 2005 Elsevier B.V. All rights reserved.