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向伏隔核微量注射尼古丁和美加明对乙醇和蔗糖自我给药的影响。

Effects of nicotine and mecamylamine microinjections into the nucleus accumbens on ethanol and sucrose self-administration.

作者信息

Nadal R, Chappell A M, Samson H H

机构信息

Department of Physiology and Pharmacology, Wake-Forest University School of Medicine, Winston-Salem, North Carolina, USA.

出版信息

Alcohol Clin Exp Res. 1998 Sep;22(6):1190-8.

PMID:9756032
Abstract

Nicotine (NIC) and ethanol (ETOH) are both drugs of abuse that can affect similar pathways in the central nervous system. However, the role of nicotinic processes in ETOH's reinforcing actions is unclear. Although the mesolimbic dopamine systems are known to be involved in the reinforcing effects of ETOH, the role of nicotinic receptors within the nucleus accumbens (NAc) in ETOH reinforcement has not been studied. To address this issue, adult male Long-Evans rats were initiated to self-administer ETOH (10% v/v, n = 14) using the sucrose-substitution procedure or sucrose (5% w/v, n = 8) in a 30-min operant session. They were then surgically implanted with bilateral stainless-steel guide cannulae to allow for microinjection into the core of the NAc. After recovery from surgery, presession microinjections of NIC (0.3, 3.3, 10, 30, and 60 microg/1 microl/brain) or the antagonist mecamylamine (MEC) (1, 3, 10, 30, and 60 microg/1 microl/brain) were performed prior to an ETOH or sucrose self-administration session. NIC (3.3 and 60 microg/microl) and MEC (30 microg/microl) both reduced ETOH self-administration behavior, without affecting sucrose-reinforced behavior. A reduction in the total duration of ETOH responding (termination) was also observed after either 60 microg/microl of NIC and 30 microg/microl of MEC. The lack of a clear dose-response relationship for the agonist and the antagonist indicates that the interaction between the NAc nicotinic system and ETOH self-administration is complex.

摘要

尼古丁(NIC)和乙醇(ETOH)都是滥用药物,它们可影响中枢神经系统中的相似通路。然而,烟碱样过程在ETOH强化作用中的角色尚不清楚。尽管已知中脑边缘多巴胺系统参与ETOH的强化作用,但伏隔核(NAc)内烟碱受体在ETOH强化中的作用尚未得到研究。为解决这一问题,成年雄性Long-Evans大鼠采用蔗糖替代程序开始自我给药ETOH(10% v/v,n = 14)或蔗糖(5% w/v,n = 8),每次操作时间为30分钟。然后通过手术给它们双侧植入不锈钢引导套管,以便向NAc核心进行微量注射。手术后恢复后,在ETOH或蔗糖自我给药前进行NIC(0.3、3.3、10、30和60微克/1微升/脑)或拮抗剂美加明(MEC)(1、3、10、30和60微克/1微升/脑)的给药前微量注射。NIC(3.3和60微克/微升)和MEC(30微克/微升)均降低了ETOH自我给药行为,而不影响蔗糖强化行为。在给予60微克/微升的NIC和30微克/微升的MEC后,还观察到ETOH反应总时长(终止)减少。激动剂和拮抗剂缺乏明确的剂量反应关系表明,NAc烟碱系统与ETOH自我给药之间的相互作用很复杂。

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