Cannabigerol improves MK-801-induced long-term recognition memory deficit in male rats through cortical TrkB-R signaling independently of changes in BDNF
Posted by Ernesto on Thursday, 27 August 2026
Autores:
Ximena López-Hill 1 , Soledad Marton 2 , Analía Richeri 3 , Sara Fabius 4 , Jessika Urbanavicius 5 , Lucía Lima de Almeida 6 , Carolina Echeverry 7 , Verónica Sánchez de Medina Baena 8 , Carlos Ferreiro 9 , Anna Castané 10 , Cecilia Scorza 11
Revista (o libro):
Pharmacol Biochem Behav.
Año:
2026
Mes-dia:
0826
issue, vol, paginas, etc:
174260
doi:
10.1016/j.pbb.2026.174260
PMID:
42648374
Abstract:
Interest in the therapeutic potential of cannabigerol (CBG), a non-psychotomimetic cannabinoid derived from Cannabis sativa, has increased recently. However, preclinical studies examining its effects on cognitive impairment, a core symptom domain of schizophrenia, remain limited. Based on the N-methyl-d-aspartate receptor (NMDA-R) hypofunction hypothesis of schizophrenia, MK-801, a potent NMDA-R antagonist, is widely used as a pharmacological model of schizophrenia that replicates the cognitive impairments observed in patients. This study investigated whether repeated systemic administration of CBG (10 mg/kg/i.p.) could reverse long-term recognition memory (LTM) impairment induced by a single dose of MK-801 (0.1 mg/kg/i.p.) in male rats, using the novel object recognition paradigm. Additionally, we evaluated whether these effects were associated with changes in BDNF/TrkB receptor (TrkB-R) signaling. ELISA and quantitative real-time PCR analyses were performed to evaluate BDNF protein levels and BDNF and TrkB-R mRNA expression in the hippocampus and medial prefrontal cortex (mPFC). MK-801 significantly impaired LTM compared with control group, whereas co-administration of CBG prevented this deficit. MK-801-induced memory impairment was associated with reduced hippocampal and cortical BDNF protein levels, without changes in BDNF or TrkB-R mRNA expression. CBG and MK-801 combined treatment did not restore BDNF mRNA expression and protein levels although it significantly increased TrkB-R mRNA expression in the mPFC. These results suggest that activation of TrkB-R signaling through a BDNF-independent mechanism may contribute to the preservation of LTM by CBG. Our results provide relevant evidence supporting the therapeutic potential of CBG for cognitive impairments associated with schizophrenia.
Afiliaciones:
1 Departmento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. Electronic address: ximenalopezhill@gmail.com.
2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Electronic address: soledadmarton@gmail.com.
3 Departmento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. Electronic address: aricheri@gmail.com.
4 Departmento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. Electronic address: sfabiusc@gmail.com.
5 Departmento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. Electronic address: jessikau@gmail.com.
6 Departmento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. Electronic address: llima@fcien.edu.uy.
7 Departmento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. Electronic address: caroliecheverry@gmail.com.
8 Phytoplant Research S.L., Cordoba, Spain. Electronic address: v.sanchez@phytoplant.es.
9 Phytoplant Research S.L., Cordoba, Spain. Electronic address: c.ferreiro@phytoplant.es.
10 School of Medicine, Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central (IRIS-CC), Spain; Department of Biomedicine, School of Medicine and Health Sciences, Institute of Neurosciences University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain. Electronic address: anna.castane@iibb.csic.es.
11 Departmento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. Electronic address: cscorza@iibce.edu.uy.
Enlace pubmed:
https://pubmed.ncbi.nlm.nih.gov/42648374/
Enlace full text:
https://doi.org/10.1016/j.pbb.2026.174260
Cita:
López-Hill X, Marton S, Richeri A, Fabius S, Urbanavicius J, de Almeida LL, Echeverry C, de Medina Baena VS, Ferreiro C, Castané A, Scorza C. Cannabigerol improves MK-801-induced long-term recognition memory deficit in male rats through cortical TrkB-R signaling independently of changes in BDNF. Pharmacol Biochem Behav. 2026 Aug 26:174260. doi: 10.1016/j.pbb.2026.174260. Epub ahead of print. PMID: 42648374.