Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors

Autor(es)

Hartmann, Alice ^{[1, 2]} ; Lisboa, Sabrina Francesca ^{[1, 2]} ; Sonego, Andreza Buzolin ^{[1, 2]} ; Coutinho, Debora ^[2] ; Gomes, Felipe Villela ^{[1, 2]} ; Guimaraes, Francisco Silveira ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo - Brazil

^[2] Univ Sao Paulo, FMRP, Med Sch Ribeirao Preto, Dept Pharmacol, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 94, AUG 30 2019.
• Citações Web of Science: 0

Resumo

Long-term single housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic, antidepressant, and antipsychotic drugs. Preclinical and clinical findings indicate that cannabidiol (CBD), a non-psychotomimetic compound from Cannabis sativa, has anxiolytic, antidepressant, and antipsychotic properties. Few studies, however, have investigated the effects of CBD on aggressive behaviors. Here, we investigated whether CBD (5, 15, 30, and 60 mg/kg; i.p.) could attenuate social isolation-induced aggressive behavior in the resident-intruder test. Male Swiss mice (7-8 weeks) were single-housed for 10 days (resident mice) to induce aggressive behaviors, while conspecific mice of same sex and age (intruder mice) were group-housed. During the test, the intruder was placed into the resident's home-cage and aggressive behaviors initiated by the resident, including the latency for the first attack, number of attacks, and total duration of aggressive encounters, were recorded. The involvement of 5-HT1A and CB1 receptors (CB1R) in the effects of CBD was also investigated. All tested CBD doses induced anti-aggressive effects, indicated by a decrease in the number of attacks. CBD, at intermediary doses (15 and 30 mg/kg), also increased latency to attack the intruder and decreased the duration of aggressive encounters. No CBD dose interfered with locomotor behavior. CBD anti-aggressive effects were attenuated by the 5-HT1A receptor antagonist WAY100635 (0.3 mg/kg) and the CB1 antagonist AM251 (1 mg/kg), suggesting that CBD decreases social isolation-induced aggressive behaviors through a mechanism associated with the activation of 5-HT1A and CB1 receptors. Also, CBD decreased c-Fos protein expression, a neuronal activity marker, in the lateral periaqueductal gray (lPAG) in social-isolated mice exposed to the resident-intruder test, indicating a potential involvement of this brain region in the drug effects. Taken together, our findings suggest that CBD may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders. (AU)

• Processo FAPESP: 16/14282-6 - Avaliação dos efeitos do canabidiol sobre as alterações neuroimunoendócrinas e comportamentais induzidas pelo estresse em camundongos
• Beneficiário: Alice Hartmann dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/17343-0 - Avaliação dos efeitos do canabidiol sobre as alterações comportamentais e moleculares induzidas pelo tratamento repetido com MK-801
• Beneficiário: Felipe Villela Gomes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/24304-0 - Novas perspectivas no emprego de fármacos que modificam neurotransmissores atípicos no tratamento de transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/22523-0 - Possíveis mecanismos neuroinflamatórios envolvidos nos déficits de extinção da resposta de medo condicionada após exposição de roedores a um predador: papel do sistema endocanabinoide
• Beneficiário: Sabrina Francesca de Souza Lisboa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/19731-6 - Identificação de mecanismos epigenéticos induzidos por estresse que modulam a sinalização endocanabinóide e a resposta neuroimunológica como novos alvos farmacológicos no tratamento do transtorno de estresse pós-traumático (PTSD)
• Beneficiário: Sabrina Francesca de Souza Lisboa
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores