Investigation of the possible antipsychotic effect of HU-910, a selective type-2 cannabinoid receptor (CB2) agonist

• Grant number: 17/09461-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2017
• Effective date (End): June 30, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Isadora Lopes Cortez
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders, AP.TEM

Abstract

Drugs used to treat schizophrenia improve mainly the positive symptoms of the disease, have low tolerability, and high rates of discontinuation of treatment. Recent evidence suggests that the endocannabinoid system may be a new target for the treatment of this disorder. The cannabinoid receptor type 2 (CB2) can modulate dopaminergic neurotransmission and attenuate the effects of proinflammatory cytokines and microglia activation, changes observed in patients with schizophrenia. The HU-910 compound, a CB2 agonist, attenuates the release of proinflammatory cytokines and injury/tissue damage in a model of ischemia. In addition, this compound reduces the hyperlocomotion induced by MK-801, an NMDA receptor antagonist, suggesting a possible antipsychotic action. Acute and chronic administration of MK-801 has been proposed as a model for studying the effects of new antipsychotics on positive, negative and cognitive symptoms of schizophrenia. Thus, the hypothesis of the present project is that HU-910, by activating CB2 receptors, would be able to reverse behaviors related to schizophrenia (memory impairment and social interaction) in a model based on repeated treatment with MK-801. In addition, we will verify the selectivity of HU-910, investigating if, at the doses where possible antipsychotic effects are detected, the drug would not produce the cannabinoid tetrad, a set of behavioral changes (analgesia, hypolocomotion, catalepsy and hypothermia) that depends on the activation of CB1 receptors. (AU)