Department of Animal Biology, School of Biology, College of Science, University of Tehran, Iran.
Addict Biol. 2013 Mar;18(2):241-51. doi: 10.1111/j.1369-1600.2011.00387.x. Epub 2011 Oct 13.
The present study evaluated the involvement of the dorsal hippocampal cannabinoid CB1 receptors in the combined effect of ethanol and nicotine on passive avoidance learning in adult male mice. The results indicated that pre-training administration of ethanol (1 g/kg, i.p.) impaired memory retrieval. Pre-test administration of ethanol (0.5 and 1 g/kg, i.p.) or nicotine (0.5 and 0.7 mg/kg, s.c.) significantly reversed ethanol-induced amnesia, suggesting a functional interaction between ethanol and nicotine. Pre-test microinjection of a selective CB1 receptor agonist, ACPA (3 and 5 ng/mouse), plus an ineffective dose of ethanol (0.25 g/kg) or nicotine (0.3 mg/kg) improved memory retrieval, while ACPA by itself could not reverse ethanol-induced amnesia. Pre-test intra-CA1 microinjection of a selective CB1 receptor antagonist, AM251 (0.5-2 ng/mouse), did not lead to a significant change in ethanol-induced amnesia. However, pre-test intra-CA1 microinjection of AM251 prevented the ethanol (1 g/kg) or nicotine (0.7 mg/kg) response on ethanol-induced amnesia. In order to support the involvement of the dorsal hippocampal CB1 receptors in nicotine response, the scheduled mixed treatments of AM251 (0.1-1 ng/mouse), ACPA (5 ng/mouse) and nicotine (0.3 mg/kg) were used. The results indicated that AM251 reversed the response of ACPA to the interactive effects of nicotine and ethanol in passive avoidance learning. Furthermore, pre-test intra-CA1 microinjection of the same doses of ACPA or AM251 had no effect on memory retrieval. These findings show that the cannabinoid CB1 receptors of dorsal hippocampus are important in the combined effect of ethanol and nicotine on passive avoidance learning.
本研究评估了背侧海马大麻素 CB1 受体在成年雄性小鼠乙醇和尼古丁联合作用对被动回避学习的影响。结果表明,预训练给予乙醇(1 g/kg,ip)可损害记忆检索。预测试给予乙醇(0.5 和 1 g/kg,ip)或尼古丁(0.5 和 0.7 mg/kg,sc)可显著逆转乙醇引起的健忘症,表明乙醇和尼古丁之间存在功能相互作用。预测试给予选择性 CB1 受体激动剂 ACPA(3 和 5 ng/只)加无效剂量乙醇(0.25 g/kg)或尼古丁(0.3 mg/kg)可改善记忆检索,而 ACPA 本身不能逆转乙醇引起的健忘症。预测试给予选择性 CB1 受体拮抗剂 AM251(0.5-2 ng/只)于 CA1 内,对乙醇引起的健忘症无明显影响。然而,预测试给予 AM251 于 CA1 内可防止乙醇(1 g/kg)或尼古丁(0.7 mg/kg)对乙醇引起的健忘症的反应。为了支持背侧海马 CB1 受体在尼古丁反应中的参与,采用了 AM251(0.1-1 ng/只)、ACPA(5 ng/只)和尼古丁(0.3 mg/kg)的预定混合处理。结果表明,AM251 逆转了 ACPA 对尼古丁和乙醇在被动回避学习中交互作用的反应。此外,预测试给予 CA1 内相同剂量的 ACPA 或 AM251 对记忆检索无影响。这些发现表明,背侧海马的大麻素 CB1 受体在乙醇和尼古丁对被动回避学习的联合作用中很重要。