title: Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice.
abstract: 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 (20 mg/kg). Moreover, repeated CBD administration at a lower dose (3 mg/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 (30 mg/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.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: Angélica Pupin
authors.initials: AP
authors.lastname: Schiavon
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: Jéssica Mendes
authors.initials: JM
authors.lastname: Bonato
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
authors.affiliation: Department of Pharmacology, School of Medicine, USP, Av. Bandeirantes, 14015-000 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Francisco Silveira
authors.initials: FS
authors.lastname: Guimarães
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil. Electronic address: rmmwoliveira@uem.br.
authors.forename: Rúbia Maria
authors.initials: RM
authors.lastname: Weffort de Oliveira
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D002185:Cannabidiol / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D011897:Random Allocation; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; C498355:Mki67 protein, mouse; D009479:Neuropeptides; D011619:Psychotropic Drugs; D002185:Cannabidiol; D007099:Imipramine
keywords: Antidepressant; Cannabidiol; Neurogenesis; Subgranular zone; Subventricular zone; Swiss mice