Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 64; pp. 27 - 34
• Main Authors: Schiavon, Angélica Pupin, Bonato, Jéssica Mendes, Milani, Humberto, Guimarães, Francisco Silveira, Weffort de Oliveira, Rúbia Maria
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 04.01.2016
• Subjects: Animals; Antidepressant; Anxiety - drug therapy; Anxiety - physiopathology; Cannabidiol; Cannabidiol - administration & dosage; Cell Proliferation - drug effects; Cell Proliferation - physiology; Dentate Gyrus - drug effects; Dentate Gyrus - physiology; Dose-Response Relationship, Drug; Emotions - drug effects; Emotions - physiology; Imipramine - pharmacology; Ki-67 Antigen - metabolism; Male; Mice; Microtubule-Associated Proteins - metabolism; Motor Activity - drug effects; Motor Activity - physiology; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neuropeptides - metabolism; Psychotropic Drugs - administration & dosage; Random Allocation; Stem Cell Niche - drug effects; Stem Cell Niche - physiology; Subgranular zone; Subventricular zone; Swiss mice; Antidepressant; OAT; DG; EPM; CBD; FTS; Subgranular zone; SGZ; CNS; Cannabidiol; H2O2; Neurogenesis; Subventricular zone; GAMA; HCl; SVZ; 5-HT1A; CUS; PBS; Swiss mice; DAB; TRPV1; GCL; OAE; TST; DNA; Δ9-THC; DCX; RMS; SEM; BrdU
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2015.06.017

Therapeutic effects of antidepressants and atypical antipsychotics may arise partially from their ability to stimulate neurogenesis. Cannabidiol (CBD), a phytocannabinoid present in Cannabis sativa, presents anxiolytic- and antipsychotic-like effects in preclinical and clinical settings. Anxiolytic-like effects of repeated CBD were shown in chronically stressed animals and these effects were parallel with increased hippocampal neurogenesis. However, antidepressant-like effects of repeated CBD administration in non-stressed animals have been scarcely reported. Here we investigated the behavioral consequences of single or repeated CBD administration in non-stressed animals. We also determined the effects of CBD on cell proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). Single CBD 3mg/kg administration resulted in anxiolytic-like effect in mice submitted to the elevated plus maze (EPM). In the tail suspension test (TST), single or repeated CBD administration reduced immobility time, an effect that was comparable to those of imipramine (20mg/kg). Moreover, repeated CBD administration at a lower dose (3mg/kg) increased cell proliferation and neurogenesis, as seen by an increased number of Ki-67-, BrdU- and doublecortin (DCX)-positive cells in both in DG and SVZ. Despite its antidepressant-like effects in the TST, repeated CBD administration at a higher dose (30mg/kg) decreased cell proliferation and neurogenesis in the hippocampal DG and SVZ. Our findings show a dissociation between behavioral and proliferative effects of repeated CBD and suggest that the antidepressant-like effects of CBD may occur independently of adult neurogenesis in non-stressed Swiss mice. •CBD has properties that are common to classic antidepressants in the tail suspension test (TST) in Swiss non-stressed mice.•CBD presents dose-dependent effects on cell proliferation and neurogenesis in the hippocampus and subventricular zone (SVZ).•The behavioral effects of repeated CBD administration may be independent of neurogenesis.