Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, 22902, USA.
Department of Psychiatry and Neurobehavioral Sciences, PO Box 801402, Charlottesville, VA, 22904, USA.
Psychopharmacology (Berl). 2019 Apr;236(4):1219-1232. doi: 10.1007/s00213-018-5128-9. Epub 2018 Nov 27.
Epidemiological data suggest that menthol may increase vulnerability to cigarette/nicotine use and relapse. While menthol's sensory properties are often attributed as the underlying cause of the enhanced vulnerability, an alternative possibility is that they are mediated via pharmacological interactions with nicotine.
This study addressed the possibility that menthol enhances nicotine intake and relapse vulnerability via pharmacological interactions with nicotine using a concurrent intravenous menthol/nicotine self-administration procedure.
Following acquisition, adolescent rats were given 23-h/day access to nicotine (0.01 mg/kg/infusion), nicotine plus menthol (0.16, 0.32, or 0.64 mg/kg/infusion), or menthol alone (0.16, 0.32, 0.64 mg/kg/infusion) for a total of 10 days. Nicotine-seeking was assessed using an extinction/cue-induced reinstatement procedure following 10 days of forced abstinence. We also assessed the effect of menthol (0.32 mg/kg/infusion) on progressive ratio responding for nicotine (0.01 mg/kg/infusion).
Menthol decreased PR responding for nicotine but did not affect self-administration under extended access conditions. The low dose of menthol tended to decrease subsequent extinction responding, and was not different from menthol alone, whereas the high dose decreased reinstatement responding. Although not significant, the highest levels of extinction responding were observed in a minority of rats in the moderate and high menthol-nicotine groups; rats in these groups also took longer to extinguish.
Taken together, these results demonstrate that pharmacological interactions of menthol with nicotine reduce, rather than increase, nicotine's reinforcing effects and some measures of relapse vulnerability. Importantly, however, moderate and high menthol doses may increase some aspects of relapse vulnerability in a minority of individuals.
流行病学数据表明，薄荷醇可能会增加对香烟/尼古丁使用和复吸的易感性。虽然薄荷醇的感官特性通常被认为是易感性增强的根本原因，但另一种可能性是，它们通过与尼古丁的药理学相互作用来介导。
本研究通过使用同时静脉内给予薄荷醇/尼古丁的自我给药程序，探讨了薄荷醇是否通过与尼古丁的药理学相互作用增强尼古丁摄入和复吸易感性的可能性。
在获得后，青少年大鼠每天 23 小时可接触尼古丁（0.01mg/kg/输注）、尼古丁加薄荷醇（0.16、0.32 或 0.64mg/kg/输注）或单独薄荷醇（0.16、0.32、0.64mg/kg/输注），共 10 天。在强制戒断 10 天后，使用消退/线索诱导复吸程序评估尼古丁寻求。我们还评估了薄荷醇（0.32mg/kg/输注）对尼古丁（0.01mg/kg/输注）进行递增比例反应的影响。
薄荷醇降低了对尼古丁的 PR 反应，但在延长接触条件下不影响自我给药。低剂量的薄荷醇倾向于减少随后的消退反应，与单独使用薄荷醇没有区别，而高剂量则减少了复吸反应。虽然不显著，但在中等和高薄荷醇-尼古丁组的少数大鼠中观察到较高的消退反应水平；这些组的大鼠也需要更长的时间来消退。
综上所述，这些结果表明，薄荷醇与尼古丁的药理学相互作用降低了尼古丁的强化作用和一些复吸易感性的测量值。然而，重要的是，中等和高剂量的薄荷醇可能会增加少数人某些方面的复吸易感性。
