Tracy H A, Wayner M J, Armstrong D L
Division of Life Sciences, The University of Texas at San Antonio, 78249-0662, USA.
Alcohol. 1999 Jun-Jul;18(2-3):123-30. doi: 10.1016/s0741-8329(98)00074-3.
Results of our previous research in rats demonstrate the following: (a) Angiotensin II (Ang II) inhibits long term potentiation (LTP) in dentate granule cell-perforant path synapses and that this inhibition can be blocked by losartan, an Ang II AT1 receptor antagonist; (b) both ethanol and diazepam inhibit LTP induction and this inhibition can be blocked by losartan; (c) impairment of air righting by ethanol and diazepam (DZ) and eight-arm radial maze performance by ethanol can be blocked by pretreatment with losartan: (d) inhibition of dentate granule cell LTP by Ang II can also be prevented by pretreatment with nicotine. Therefore, it seemed reasonable to hypothesize that ethanol and diazepam impairment of air righting and maze performance might also be blocked by pretreatment with nicotine. The purpose of the present study was to determine the effects of nicotine 0.1, 0.2, 0.3, and 0.4 mg/kg subcutaneously (SC) on 2.0 g/kg ethanol per os (PO) and 1.0 and 2.0 mg/kg DZ intraperitoneally (i.p.) induced impairment of air righting; and to determine if the impaired maze performance due to 2.0 g/kg ethanol PO could be prevented by pretreatment with 0.4 mg/kg of nicotine, SC. Results confirm the hypothesis that moderate doses of ethanol, 2.0 g/kg PO, and DZ, 1.0 mg/kg i.p. impair air righting and that the impairment can be prevented by pretreatment with nicotine SC. Nicotine was not effective in blocking the 2.0 mg/kg DZ impairment of air righting. Nicotine, 0.4 mg/kg SC, prevented the impaired maze performance induced by 2.0 g/kg ethanol PO.
(a) 血管紧张素II（Ang II）抑制齿状颗粒细胞-穿通通路突触中的长时程增强（LTP），且这种抑制可被Ang II AT1受体拮抗剂氯沙坦阻断；(b) 乙醇和地西泮均抑制LTP的诱导，且这种抑制可被氯沙坦阻断；(c) 乙醇和地西泮（DZ）对翻正反射的损害以及乙醇对八臂放射状迷宫表现的损害可通过氯沙坦预处理来阻断：(d) 用尼古丁预处理也可防止Ang II对齿状颗粒细胞LTP的抑制。因此，推测乙醇和地西泮对翻正反射和迷宫表现的损害也可能通过尼古丁预处理来阻断似乎是合理的。本研究的目的是确定皮下注射（SC）0.1、0.2、0.3和0.4 mg/kg尼古丁对经口（PO）给予2.0 g/kg乙醇和腹腔注射（i.p.）1.0和2.0 mg/kg DZ诱导的翻正反射损害的影响；并确定皮下注射0.4 mg/kg尼古丁预处理是否可预防经口给予2.0 g/kg乙醇所致的迷宫表现受损。结果证实了以下假设：中等剂量的乙醇（经口给予2.0 g/kg）和地西泮（腹腔注射1.0 mg/kg）会损害翻正反射，且这种损害可通过皮下注射尼古丁预处理来预防。尼古丁对阻断2.0 mg/kg地西泮所致的翻正反射损害无效。皮下注射0.4 mg/kg尼古丁可预防经口给予2.0 g/kg乙醇所致的迷宫表现受损。
