The involvement of mesolimbic dopamine system in cotinine self-administration in rats.
The involvement of mesolimbic dopamine system in cotinine self-administration in rats.
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DOI：
10.1016/j.bbr.2021.113596
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发表时间：
2022-01-24
影响因子：
2.7
通讯作者：
Ding ZM
中科院分区：
文献类型：
--
作者：
Tan X;Ingraham CM;McBride WJ;Ding ZM
可替宁是尼古丁的主要代谢物，最近已被证明可由大鼠自行静脉注射。然而，可替宁自我给药的机制尚不清楚。从腹侧被盖区（VTA）到伏隔核（NAC）的中边缘多巴胺系统与包括尼古丁在内的药物强化密切相关。本研究的目的是确定中脑边缘多巴胺系统在可替宁自我给药中的潜在作用。颅内自给药实验表明，大鼠可替宁以0.88和1.76 ng/100 nl/次的剂量自输于VTA。大鼠在可替宁获得过程中产生的活性杠杆比非活性杠杆反应多，在可替宁被载体替代后反应减少，在再次接触可替宁时反应恢复。可替宁以1.76 ng/100 nl/滴入VTA可增加NAC内的细胞外多巴胺水平。皮下注射1mg /kg的可替宁也增加了NAC内的细胞外多巴胺水平。注射d1样受体拮抗剂SCH 23390可减少静脉注射可替宁的自我给药。另一方面，安非他酮，一种儿茶酚胺摄取抑制剂，没有显著改变静脉注射可替宁的自我给药。这些结果表明，中边缘多巴胺系统的激活可能是可替宁自我给药的一种细胞机制。可替宁和尼古丁之间的这种共同机制表明，可替宁可能在尼古丁强化中起作用。
Cotinine is the major metabolite of nicotine and has recently been shown to be self-administered intravenously by rats. However, mechanisms underlying cotinine self-administration remained unknown. Mesolimbic dopamine system projecting from the ventral tegmental area (VTA) to nucleus accumbens (NAC) is closely implicated in drug reinforcement, including nicotine. The objective of the current study was to determine potential involvement of mesolimbic dopamine system in cotinine self-administration. An intracranial self-administration experiment demonstrates that cotinine at 0.88 and 1.76 ng/100 nl/infusion was self-infused into the VTA by rats. Rats produced more infusions of cotinine than vehicle and responded more on active than inactive lever during acquisition, reduced responding when cotinine was replaced by vehicle, and resumed responding during re-exposure to cotinine. Microinjection of cotinine at 1.76 ng/100 nl/infusion into the VTA increased extracellular dopamine levels within the NAC. Subcutaneous injection of cotinine at 1 mg/kg also increased extracellular dopamine levels within the NAC. Administration of the D1-like receptor antagonist SCH 23390 attenuated intravenous cotinine self-administration. On the other hand, bupropion, a catecholamine uptake inhibitor, did not significantly alter intravenous cotinine self-administration. These results suggest that activation of mesolimbic dopamine system may represent one cellular mechanism underlying cotinine self-administration. This shared mechanism between cotinine and nicotine suggests that cotinine may play a role in nicotine reinforcement.
影响因子：
3.4
作者：
Hauser SR;Bracken AL;Deehan GA Jr;Toalston JE;Ding ZM;Truitt WA;Bell RL;McBride WJ;Rodd ZA
通讯作者：
Rodd ZA