Cannabidiol injected into the bed nucleus of the stria terminalis modulates baroreflex activity through 5-HT1A receptors

Abstract: Cannabidiol (CBD) is a non-psychotomimetic constituent of the Cannabis sativa plant that inhibits behavioral and cardiovascular responses to aversive situations, facilitating 5-HT1A-mediated neurotransmission. Previous results from our group suggest that the bed nucleus of the stria terminalis (BNST) may be involved in CBD''s anti-aversive effects. To investigate whether the cardiovascular effects of the CBD could involve a direct drug effect on the BNST, we evaluated the effects of CBD microinjection into this structure on baroreflex activity. We also verified whether these effects were mediated by the activation of 5-HT1A receptors. Bilateral microinjection of CBD (60nmol/100nL) into the BNST increased the bradycardiac response to arterial pressure increases. However, no changes were observed in tachycardiac responses evoked by arterial pressure decreases. Pretreatment of the BNST with the selective 5-HT1A receptor antagonist WAY100635 (0.37nmol/100nL) prevented CBD effects on the baroreflex activity. Moreover, microinjection of the 5-HT1A receptor agonist 8-OH-DPAT (4nmol/100nL) caused effects that were similar to those observed after the microinjection of CBD, which were also blocked by pretreatment with WAY100635. In conclusion, the present studies show that the microinjection of CBD into the BNST has a facilitatory influence on the baroreflex response to blood pressure increases, acting through the activation of 5-HT1A receptors. [Copyright &y& Elsevier]