The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in female rats.
The effects of varenicline on methamphetamine self-administration and drug-primed reinstatement in female rats.
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DOI：
10.1016/j.bbr.2015.11.033
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发表时间：
2016-03-01
影响因子：
2.7
通讯作者：
Bevins RA
中科院分区：
文献类型：
--
作者：
Pittenger ST;Barrett ST;Chou S;Bevins RA
虽然研究表明女性对冰毒成瘾的脆弱性更高，但临床前模型在调查冰毒寻求和复发时很少使用女性受试者。本研究的目的是检查伐尼克兰（Chantix®）（一种部分α4β2和完全α7烟碱乙酰胆碱受体激动剂）对雌性大鼠自我给药和恢复的影响。Sprague-Dawley大鼠手术植入留置颈静脉导管。然后训练一半的大鼠以可变比率3强化时间表自我施用甲基（0.056 mg/kg/输注）;另一半在每天2小时的会话期间获得静脉内生理盐水。当反应稳定时，测试伐尼克兰（0.0、0.3、1.0、3.0 mg/kg）以确定它如何改变甲安菲他汀服用。在4个测试日探测伐尼克兰;每个测试由2个标准自我给药阶段分开，以确保反应保持稳定。在此测试之后，进行了15次灭绝会话。在最后一次灭绝会议之后的24小时，是连续四天的甲基引发恢复。检查了相同的4剂伐尼克兰，以确定它如何改变0.3 mg/kg冰毒（IP）引发的恢复。老鼠很容易自我注射冰毒。较高剂量的伐尼克兰并没有以特定的方式影响甲基摄入，因为在自我给药阶段获得盐水的大鼠中，主动杠杆按压也略有减少。雌性大鼠表现出强大的甲基引发的恢复。值得注意的是，较低剂量的伐尼克兰增加了甲基引发的恢复。这种放大的复原敏感性（即，复发）可能是使用伐尼克兰作为治疗剂治疗冰毒使用障碍的障碍。
While research has revealed heightened vulnerability to meth addiction in women, preclinical models rarely use female subjects when investigating meth seeking and relapse. The goal of the present study was to examine the effects of varenicline (Chantix®), a partial α4β2 and full α7 nicotinic acetylcholine receptor agonist, on meth self-administration and reinstatement in female rats. Sprague-Dawley rats were surgically implanted with an indwelling jugular catheter. Half of the rats were then trained to self-administer meth (0.056 mg/kg/infusion) on a variable ratio 3 schedule of reinforcement; the other half earned intravenous saline during daily, 2 hour sessions. When responding stabilized, varenicline (0.0, 0.3, 1.0, 3.0 mg/kg) was tested to determine how it altered meth taking. Varenicline was probed on 4 test days; each test separated by 2 standard self-administration sessions to assure responding remained stable. Following this testing was 15 extinction sessions. Twenty-four hours after the last extinction session were four consecutive days of meth-primed reinstatement. The same 4 doses of varenicline were examined to determine how it altered reinstatement triggered by 0.3 mg/kg meth (IP). Rats readily self-administered meth. The higher doses of varenicline did not affect meth-taking in a specific fashion as active lever pressing wasalso slightly reduced in rats that has access to saline in the self-administration phase. Female rats displayed robust meth-primed reinstatement. Notably, the lower doses of varenicline increased meth-primed reinstatement. This amplified susceptibility to reinstatement (i.e., relapse) may be an impediment for the use of varenicline as a therapeutic to treat meth use disorder.