Relapse to cotinine seeking in rats: differential effects of sex.
Relapse to cotinine seeking in rats: differential effects of sex.
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DOI：
10.1097/fbp.0000000000000696
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发表时间：
2022-10-01
影响因子：
1.6
通讯作者：
Ding, Zheng-Ming
中科院分区：
文献类型：
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作者：
Tan, Xiaoying;Neslund, Elizabeth;Ding, Zheng-Ming
复吸是吸烟的一个特征，也是戒烟管理的一个重大挑战。阐明复发的新因素可能会为未来的治疗提供信息。尼古丁的主要代谢产物可替宁已被证明支持大鼠静脉自我给药，表明其是促进尼古丁强化的一个潜在因素。然而，目前尚不清楚可替宁是否会诱导复发样行为。本研究调查了两种复吸模型中可替宁寻求的复吸，即药物寻求的恢复和药物渴望模型的孵化。在恢复模型中，训练大鼠自我给予可替宁，经历可替宁相关反应的消退，并测试线索、药物或应激诱导的恢复。与可替宁自我给药、可替宁（1-2 mg/kg）或药理应激物育亨宾（1.25-2.5 mg/kg）相关的条件性提示诱导可替宁寻求的恢复。雌性大鼠表现出更明显的线索诱导，但不是药物或压力诱导的恢复比雄性大鼠。在渴求模型的孵化中，训练大鼠自我给予可替宁，并在家中笼中进行强制戒断。在停药第1天和停药第18天测试大鼠的线索诱导的可替宁寻找。与停药第1天相比，大鼠在停药第18天表现出更大的线索诱导的可替宁寻找，雄性和雌性大鼠之间无差异。这些结果表明，可替宁诱导大鼠的药物寻求性复发，表明可替宁可能有助于复发。
Relapse is a defining feature of smoking and a significant challenge in cessation management. Elucidation of novel factors underlying relapse may inform future treatments. Cotinine, the major metabolite of nicotine, has been shown to support intravenous self-administration in rats, implicating it as one potential factor contributing to nicotine reinforcement. However, it remains unknown whether cotinine would induce relapse-like behaviors. The current study investigated relapse to cotinine seeking in two relapse models, the reinstatement of drug seeking and incubation of drug craving models. In the reinstatement model, rats were trained to self-administer cotinine, underwent extinction of cotinine-associated responses, and were tested for cue-, drug-, or stress-induced reinstatement. Conditioned cues associated with cotinine self-administration, cotinine (1–2 mg/kg), or the pharmacological stressor yohimbine (1.25–2.5 mg/kg) induced reinstatement of cotinine seeking. Female rats displayed more pronounced cue-induced, but not drug- or stress-induced reinstatement than male rats. In the incubation of craving model, rats were trained to self-administer cotinine and underwent forced withdrawal in home cages. Rats were tested for cue-induced cotinine seeking on both withdrawal day 1 and withdrawal day 18. Rats exhibited greater cue-induced cotinine-seeking on withdrawal day 18 compared to withdrawal day 1, with no difference between male and female rats. These findings indicate that cotinine induces sex-specific relapse to drug seeking in rats, suggesting that cotinine may contribute to relapse.