Adaptations in cholinergic transmission in the ventral tegmental area associated with the affective signs of nicotine withdrawal in rats
Adaptations in cholinergic transmission in the ventral tegmental area associated with the affective signs of nicotine withdrawal in rats
复制标题
DOI：
10.1016/j.neuropharm.2004.05.005
复制
发表时间：
2004-09-01
影响因子：
4.7
通讯作者：
Markou, A
中科院分区：
文献类型：
--
作者：
Bruijnzeel, AW;Markou, A
长期给予尼古丁会诱导大脑奖赏回路中的适应性变化，以抵消急性药物作用;当停止给予尼古丁时，这些适应性变化仍然不受阻碍，并导致药物戒断。本研究旨在探讨慢性尼古丁给药对腹侧被盖区（VTA）和延髓核壳（Nacc）烟碱型乙酰胆碱受体（nAChR）活性的影响。在大鼠中使用了一种离散试验颅内自我刺激程序，该程序提供了电流强度阈值作为脑奖励功能的测量。先前的研究表明，戒断尼古丁会导致大脑奖励阈值升高，这表明大脑奖励功能下降。我们在这里表明，注射nAChR拮抗剂二氢-β-赤藓定（DH E; 0.6-20 μ g总双边剂量）到腹侧被盖区，但不是腹侧被盖区外，导致在尼古丁依赖大鼠（9毫克/公斤/天尼古丁酒石酸氢盐）的大脑奖励阈值显着升高，而没有在盐水处理的控制。相比之下，DHPE（0.6-20 μ g总双边剂量）注射到Nacc壳对尼古丁或盐水处理的大鼠的大脑奖励阈值没有影响。腹侧被盖区胆碱能传递的适应性变化可能至少部分地介导了人类尼古丁戒断的情感体征。(C)2004爱思唯尔有限公司保留所有权利。
Chronic administration of nicotine induces adaptations in the brain reward circuit to counteract the acute drug effects; when nicotine administration ceases, these adaptations remain unopposed and lead to drug withdrawal. The present studies were conducted to assess the effects of chronic nicotine administration on nicotinic acetylcholine receptor (nAChR) activity in the ventral tegmental area (VTA) and the nucleus accumbens (Nacc) shell. A discrete-trial intracranial self-stimulation procedure that provides current-intensity thresholds as measures of brain reward function was used in rats. Previous studies have shown that withdrawal from nicotine-induced elevations in brain reward thresholds that are indicative of a decrease in brain reward function. We show here that injections of the nAChR antagonist dihydro-beta-erythroidine (DH E; 0.6-20 mug total bilateral dose) into the VTA, but not outside the VTA, resulted in significant elevations in brain reward thresholds in nicotine dependent rats (9 mg/kg/day nicotine hydrogen tartrate) while having no effect in saline-treated controls. By contrast, DHPE (0.6-20 mug total bilateral dose) injected into the Nacc shell had no effect on brain reward thresholds of nicotine- or saline-treated rats. The adaptations in cholinergic transmission in the VTA are likely to mediate, at least partly, the affective signs of nicotine withdrawal in humans. (C) 2004 Elsevier Ltd. All rights reserved.