Uhernik A L, Montoya Z T, Balkissoon C D, Smith J P
Colorado State University-Pueblo, United States.
Colorado State University-Pueblo, United States.
Neurobiol Learn Mem. 2018 Mar;149:68-76. doi: 10.1016/j.nlm.2018.02.009. Epub 2018 Feb 9.
Cannabidiol (CBD) is thought to have therapeutic potential for treating psychiatric conditions that affect cognitive aspects of learning and memory, including anxiety and post-traumatic stress disorder (PTSD). Studies have shown that CBD enhances extinction of fear memory when given after conditioning. This led us to hypothesize that CBD, if administered prior to fear conditioning, might modulate cognitive learning and memory processes in additional ways that would further guide its potential use for treating PTSD. Therefore, we designed a study to investigate effects of CBD on fear learning and memory when administered to mice prior to administering a trace fear conditioning protocol which imposes cognitive demands on the learning and memory process. We show that CBD-treated animals had increased levels of freezing during conditioning, enhanced generalized fear, inhibited cue-dependent memory extinction, slightly increased levels of freezing during an auditory-cued memory test, and increased contextual fear memory. Because synaptic plasticity is the fundamental mechanism of learning and memory, we also evaluated the impact of CBD on trace conditioning-dependent dendritic spine plasticity which occurred in the dorsal lateral amygdala and CA1 region of the ventral hippocampus. We showed that CBD mildly enhanced spine densities independent of conditioning, and inhibited conditioning-dependent spine increases in the hippocampi, but not the amygdala of fear conditioned animals. Overall, the memory-modulating effects of a single pre-conditioning dose of CBD, which we show here, demonstrate the need to more fully characterize its basic effects on memory, suggest caution when using it clinically as an anxiolytic, and point to a need for more research into its potential as a therapeutic for treating memory-loss disorders.
大麻二酚（CBD）被认为在治疗影响学习和记忆认知方面的精神疾病方面具有治疗潜力，包括焦虑症和创伤后应激障碍（PTSD）。研究表明，在条件反射后给予CBD可增强恐惧记忆的消退。这使我们推测，如果在恐惧条件反射之前给予CBD，可能会以其他方式调节认知学习和记忆过程，从而进一步指导其在治疗PTSD方面的潜在用途。因此，我们设计了一项研究，以调查在对小鼠进行痕量恐惧条件反射实验（该实验对学习和记忆过程提出了认知要求）之前给予CBD对恐惧学习和记忆的影响。我们发现，接受CBD治疗的动物在条件反射过程中的僵立水平增加，全身性恐惧增强，线索依赖性记忆消退受到抑制，在听觉线索记忆测试中的僵立水平略有增加，情境恐惧记忆增强。由于突触可塑性是学习和记忆的基本机制，我们还评估了CBD对痕量条件反射依赖性树突棘可塑性的影响，这种可塑性发生在腹侧海马体的背外侧杏仁核和CA1区域。我们发现，CBD在与条件反射无关的情况下轻度增强了树突棘密度，并抑制了恐惧条件反射动物海马体中与条件反射相关的树突棘增加，但杏仁核中未出现这种情况。总体而言，我们在此展示的单次预处理剂量的CBD的记忆调节作用表明，有必要更全面地描述其对记忆的基本影响，临床使用时作为抗焦虑药需谨慎，并指出需要对其作为治疗记忆丧失障碍的疗法的潜力进行更多研究。
