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Role of hippocampal and prefrontal cortical cholinergic transmission in combination therapy valproate and cannabidiol in memory consolidation in rats: involvement of CREB- BDNF signaling pathways.
- Source :
- Naunyn-Schmiedeberg's Archives of Pharmacology; Jul2024, Vol. 397 Issue 7, p5029-5047, 19p
- Publication Year :
- 2024
-
Abstract
- Purpose: Cognitive disorders are associated with valproate and drugs used to treat neuropsychological diseases. Cannabidiol (CBD) has beneficial effects on cognitive function. This study examined the effects of co-administration of CBD and valproate on memory consolidation, cholinergic transmission, and cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway in the prefrontal cortex (PFC) and hippocampus (HPC). Methods: One-trial, step-through inhibitory test was used to evaluate memory consolidation in rats. The intra-CA1 injection of physostigmine and atropine was performed to assess the role of cholinergic transmission in this co-administration. Phosphorylated CREB (p-CREB)/CREB ratio and BDNF levels in the PFC and HPC were evaluated. Results: Post-training intraperitoneal (i.p.) valproate injection reduced memory consolidation; however, post-training co-administration of CBD with valproate ameliorated memory impairment induced by valproate. Post-training intra-CA1 injection of physostigmine at the ineffective doses in memory consolidation (0.5 and 1 µg/rat), plus injection of 10 mg/kg of CBD as an ineffective dose, improved memory loss induced by valproate, which was associated with BDNF and p-CREB level enhancement in the PFC and HPC. Conversely, post-training intra-CA1 injection of ineffective doses of atropine (1 and 2 µg/rat) reduced the positive effects of injection of CBD at a dose of 20 mg/kg on valproate-induced memory loss associated with BDNF and p-CREB level reduction in the PFC and HPC. Conclusion: The results indicated a beneficial interplay between valproate and CBD in the process of memory consolidation, which probably creates this interaction through the BDNF-CREB signaling pathways in the cholinergic transmission of the PFC and HPC regions. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00281298
- Volume :
- 397
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Naunyn-Schmiedeberg's Archives of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 177797067
- Full Text :
- https://doi.org/10.1007/s00210-023-02941-4