New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders

• Grant number: 17/24304-0
• Support type: Research Projects - Thematic Grants
• Duration: February 01, 2019 - January 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Francisco Silveira Guimaraes
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Co-Principal Investigators: Elaine Aparecida Del Bel Belluz Guimarães ; Leonardo Resstel Barbosa Moraes ; Sâmia Regiane Lourenço Joca
• Assoc. researchers: Alline Cristina de Campos ; Ana Carolina de Castro Issy Pereira ; Ana Luisa Bernardes Terzian ; Antonio Cardozo dos Santos ; Ariandra Guerini Sartim ; Claudia Maria de Castro Batista ; Cristina Aparecida Jark Stern ; Daniele Cristina de Aguiar ; Elaine Aparecida Del Bel Belluz Guimarães ; Fabricio de Araujo Moreira ; Fernanda Grecco Grano ; Fernando Morgan de Aguiar Correa ; Frederico Rogério Ferreira ; Glauce Crivelaro Do Nascimento ; Leandro José Bertoglio ; Mariza Bortolanza ; Maurício dos Santos Pereira ; Nilson Carlos Ferreira Junior ; Pedro Henrique Gobira Nunes ; Rúbia Maria Monteiro Weffort de Oliveira ; Sabrina Francesca de Souza Lisboa
• Associated scholarship(s): 20/02297-4 - Conditioned and unconditioned stimulus send at fixed or randomized intervals: possible behavioral differences for the expression and extinction of conditioned fear memory, BP.IC; 20/04145-7 - Investigation of the possible involvement of adenosinergic receptors in the behavioral effects induced by cannabidiol in mice using different animal models, BP.IC; 19/26351-0 - Evaluation of paclitaxel-induced cognitive deficits in a 4T-1 murine mammary carcinoma model and possible protective effect of concomitant cannabidiol treatment, BP.IC; + associated scholarships 19/24591-4 - Mechanisms of cannabidiol antipsychotics effects in schizophrenia model based in neurodevelopment variation, BP.DR; 19/18846-0 - Role of the endocannabinoid system in orofacial muscular pain related to Parkinson's Disease, BP.IC; 19/26810-5 - Extracellular vesicles as signals of the hippocampal neurogenic niche: participation in the behavioral effects of cannabinoid and antidepressant drugs, BP.PD; 18/15896-3 - Participation of DNA methylation in rapid and sustained antidepressant-like effects induced by Cannabidiol and Ketamine, BP.PD; 18/20433-2 - Neuroprotective and behavioral effects of the PPAR³ agonist pioglitazone in a neurodevelopmental model of schizophrenia, BP.PD; 17/14207-7 - THE ACTION OF CANNABINOID DRUGS IN L-DOPA-INDUCED DISCINESIA: ANALYSIS OF NEUROINFLAMATION AND GLUTAMATE RELEASE IN GLIAL CELLS, BP.PD - associated scholarships

Abstract

The need to develop new therapeutic targets for the treatment of neuropsychiatric disorders is a consensus in the scientific literature. Endocannabinoids (eCBs) and nitric oxide (NO) have been proposed as two of these possible targets. Studies from our group have disclosed the therapeutic potential of drugs that interfere with these two atypical neurotransmitters in anxiety, depressive, psychotic disorders, Parkinson's disease, aggressive behavior and neurodegeneration/neurotoxicity. Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid, which, among other effects, can increase the levels of the eCB anandamide, is already undergoing clinical trials to test its efficacy in some of these disorders. However, several important questions still remain related to the therapeutic potential of these drugs in other specific disorders as well as to the mechanisms involved. In the last few years our studies have indicated new possibilities, including facilitation of adult hippocampal neurogenesis and autophagy and the possible involvement of neuroinflammatory/neuroimmune mechanisms. The present project aimed at continuing this research line, trying to investigate 1. Which is the involvement and mechanisms of the anti-inflammatory effects of CBD and drugs that modify the NO and eCB system in their potential therapeutic effects?; 2. Which other neuropsychiatric disorders could benefice from these drugs?; 3. In case of co-morbities such as metabolic syndrome and anxiety disorders, in which an inflammatory component is present, would these new therapies be effective?; 4. Which other intra-cellular pathways would be involved?; 5. Which is the specific eCB involvement in the modulation of rewarding and aversive responses?; 6. Which specific epigenetic mechanisms are involved with these effects? (AU)

Scientific publications

(11)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HEIMANN, ANDREA S.; DALE, CAMILA S.; GUIMARAES, FRANCISCO S.; REIS, RICARDO A. M.; NAVON, AMI; SHMUELOV, MICHAL A.; RIOLI, VANESSA; GOMES, IVONE; DEVI, LAKSHMI L.; FERRO, EMER S. Hemopressin as a breakthrough for the cannabinoid field. Neuropharmacology, v. 183, FEB 1 2021. Web of Science Citations: 0.

DOS SANTOS PEREIRA, MAURICIO; ABREU, GABRIEL HENRIQUE DIAS; ROCCA, JEREMY; HAMADAT, SABAH; RAISMAN-VOZARI, RITA; MICHEL, PATRICK PIERRE; DEL BEL, ELAINE. Contributive Role of TNF-alpha to L-DOPA-Induced Dyskinesia in a Unilateral 6-OHDA Lesion Model of Parkinson's Disease. FRONTIERS IN PHARMACOLOGY, v. 11, JAN 11 2021. Web of Science Citations: 0.

ASTH, LAILA; IGLESIAS, LIA P.; BRIANIS, RAYSSA C.; MARCAL, ANNA P.; SOARES, NICIA P.; AGUIAR, DANIELE C.; MOREIRA, FABRICIO A. Effects of the monoamine stabilizer, (-)-OSU6162, on cocaine-induced locomotion and conditioned place preference in mice. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, JAN 2021. Web of Science Citations: 0.

MACIEL, IZAQUE DE SOUSA; SALES, AMANDA J.; CASAROTTO, PLINIO C.; CASTREN, EERO; BIOJONE, CAROLINE; JOCA, SAMIA R. L. Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats. European Journal of Neuroscience, DEC 2020. Web of Science Citations: 0.

GONZALEZ-LIZARRAGA, FLORENCIA L.; PLOPER, DIEGO; AVILA, CESAR L.; SOCIAS, SERGIO B.; DOS-SANTOS-PEREIRA, MAURICIO; MACHIN, BELEN; DEL-BEL, ELAINE; MICHEL, PATRICK PIERRE; PIETRASANTA, I, LIA; RAISMAN-VOZARI, RITA; CHEHIN, ROSANA. CMT-3 targets different alpha-synuclein aggregates mitigating their toxic and inflammogenic effects. SCIENTIFIC REPORTS, v. 10, n. 1 NOV 20 2020. Web of Science Citations: 0.

CORTEZ, ISADORA L.; RODRIGUES DA SILVA, NAIELLY; GUIMARAES, FRANCISCO S.; GOMES, FELIPE V. Are CB2 Receptors a New Target for Schizophrenia Treatment?. FRONTIERS IN PSYCHIATRY, v. 11, OCT 30 2020. Web of Science Citations: 0.

ULIANA, DANIELA L.; ANTERO, LEANDRO S.; BORGES-ASSIS, ANNA B.; ROSA, JESSICA; VILA-VERDE, CARLA; LISBOA, SABRINA F.; RESSTEL, LEONARDO B. M. Differential modulation of the contextual conditioned emotional response by CB1 and TRPV1 receptors in the ventromedial prefrontal cortex: Possible involvement of NMDA/nitric oxide-related mechanisms. JOURNAL OF PSYCHOPHARMACOLOGY, v. 34, n. 9 JUL 2020. Web of Science Citations: 0.

DA SILVA, NAIELLY RODRIGUES; GOMES, FELIPE VILLELA; SONEGO, ANDREZA BUZOLIN; DA SILVA, NICOLE RODRIGUES; GUIMARAES, FRANCISCO SILVEIRA. Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors. PHARMACOLOGICAL RESEARCH, v. 156, JUN 2020. Web of Science Citations: 0.

RAYMUNDI, ANA MARIA; DA SILVA, THIAGO R.; ZAMPRONIO, ALEKSANDER R.; GUIMARAES, FRANCISCO S.; BERTOGLIO, LEANDRO J.; STERN, CRISTINA A. J. A time-dependent contribution of hippocampal CB1, CB2 and PPAR gamma receptors to cannabidiol-induced disruption of fear memory consolidation. British Journal of Pharmacology, v. 177, n. 4, SI JAN 2020. Web of Science Citations: 0.

LOPES, JADNA B.; BASTOS, JULIANA R.; COSTA, RAYSSA B.; AGUIAR, DANIELE C.; MOREIRA, FABRICIO A. The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice. Psychopharmacology, OCT 2019. Web of Science Citations: 0.

HARTMANN, ALICE; LISBOA, SABRINA FRANCESCA; SONEGO, ANDREZA BUZOLIN; COUTINHO, DEBORA; GOMES, FELIPE VILLELA; GUIMARAES, FRANCISCO SILVEIRA. Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 94, AUG 30 2019. Web of Science Citations: 0.