Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14090-090, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
Eur Neuropsychopharmacol. 2013 Sep;23(9):1096-104. doi: 10.1016/j.euroneuro.2012.09.007. Epub 2012 Oct 4.
Systemic administration of cannabidiol (CBD) is able to attenuate cardiovascular responses to acute restraint stress through activation of 5-HT1A receptors. Previous results from our group suggest that the bed nucleus of the stria terminalis (BNST) is involved in the antiaversive effects of the CBD. Moreover, it has been proposed that synapses within the BNST influence restraint-evoked cardiovascular changes, in particular by an inhibitory influence on the tachycardiac response associated to restraint stress. Thus, the present work investigated the effects of CBD injected into the BNST on cardiovascular changes induced by acute restraint stress and if these effects would involve the local activation of 5-HT1A receptors. The exposition to restraint stress increased both blood pressure and heart rate (HR). The microinjection of CBD (30 and 60 nmol) into the BNST enhanced the restraint-evoked HR increase, in a dose-dependent manner, without affecting the pressor response. The selective 5-HT1A receptor antagonist WAY100635 by itself did not change the cardiovascular responses to restraint stress, but blocked the effects of CBD. These results showed that CBD microinjected into the BNST enhanced the HR increase associated with acute restraint stress without affecting the blood pressure response. Although these results are not in agreement with those observed after systemic administration of CBD, they are similar to effects observed after reversible inactivation of the BNST. Moreover, similar to the effects observed after systemic administration, CBD effects in the BNST seem to depend on activation of 5-HT1A receptors.
系统给予大麻二酚（CBD）能够通过激活 5-HT1A 受体来减轻急性束缚应激引起的心血管反应。我们之前的研究结果表明，终纹床核（BNST）参与了 CBD 的抗焦虑作用。此外，有人提出 BNST 内的突触会影响束缚引起的心血管变化，特别是通过对与束缚应激相关的心动过速反应的抑制作用。因此，本研究调查了 BNST 内注射 CBD 对急性束缚应激引起的心血管变化的影响，以及这些影响是否涉及局部激活 5-HT1A 受体。暴露于束缚应激会增加血压和心率（HR）。BNST 内微注射 CBD（30 和 60 nmol）以剂量依赖性方式增强束缚引起的 HR 增加，而不影响升压反应。选择性 5-HT1A 受体拮抗剂 WAY100635 本身不会改变束缚应激引起的心血管反应，但会阻断 CBD 的作用。这些结果表明，BNST 内注射 CBD 增强了与急性束缚应激相关的 HR 增加，而不影响血压反应。尽管这些结果与系统给予 CBD 后观察到的结果不一致，但它们与 BNST 可逆失活后观察到的效应相似。此外，与系统给予 CBD 后的作用相似，BNST 中的 CBD 作用似乎依赖于 5-HT1A 受体的激活。
