| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 4312244 | Behavioural Brain Research | 2016 | 10 Pages |
•CBD administration into the rat vmPFC, either into PL or IL, reduced the immobility time in the forced swimming test, an antidepressant-like effect.•The administration of 8-OH-DPAT, a 5-HT1A agonist, into PL or IL induced antidepressant-like effects similar to CBD.•CBD-induced antidepressant-like effects were blocked by local pretreatment with WAY100635, a 5-HT1A receptor antagonist.
RationaleSystemic administration of cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects. The mechanism of action of CBD is thought to involve the activation of 5-HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation. The brain regions involved in CBD-induced antidepressant-like effects remain unknown. The ventral medial prefrontal cortex (vmPFC), which includes the infralimbic (IL) and prelimbic (PL) subregions, receives dense serotonergic innervation and plays a significant role in stress responses.ObjectiveTo test the hypothesis that the administration of CBD into the IL or PL would induce an antidepressant-like effect through 5-HT1A and CB1 activation.MethodsRats received intra-IL or -PL microinjections of CBD (10–60 nmol/side), 8-OH-DPAT (5-HT1A agonist, 5–10 nmol/side), anandamide (AEA, 0.5 pmol/side) or vehicle (0.2 μl/side) and were submitted to the forced swimming (FST) or to the open field (OFT) tests. Independent CBD-treated groups were pre-treated with WAY100635 (10, 30 nmol/side, 5-HT1A antagonist) or AM251 (10 pmol/side, CB1 antagonist) and submitted to the same tests. An additional group was treated with WAY100635 followed by anandamide.ResultsCBD (PL: 10–60 nmol; IL:45–60 nmol) and 8-OH-DPAT (10 nmol) administration significantly reduced the immobility time in the FST, without changing locomotor activity in the OFT. WAY100635 (30 nmol) did not induce effect per se but blocked CBD, 8-OH-DPAT and AEA effects. Additionally, AM251 blocked CBD-effects.Conclusionadministration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors.
