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.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE

Original Publication: Berlin, New York, Springer Verlag.

Valproic Acid*/administration & dosage ; Valproic Acid*/pharmacology ; Brain-Derived Neurotrophic Factor*/metabolism ; Prefrontal Cortex*/drug effects ; Prefrontal Cortex*/metabolism ; Signal Transduction*/drug effects ; Cannabidiol*/pharmacology ; Cannabidiol*/administration & dosage ; Cyclic AMP Response Element-Binding Protein*/metabolism ; Hippocampus*/drug effects ; Hippocampus*/metabolism ; Rats, Wistar* ; Memory Consolidation*/drug effects; Animals ; Male ; Rats ; Drug Therapy, Combination ; Synaptic Transmission/drug effects

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.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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1400-1-4-18436 Iran University of Medical Sciences

Keywords: BDNF; CREB; Cannabidiol; Hippocampus; Prefrontal Cortex; Valproate

614OI1Z5WI (Valproic Acid)
0 (Brain-Derived Neurotrophic Factor)
19GBJ60SN5 (Cannabidiol)
0 (Cyclic AMP Response Element-Binding Protein)
0 (Bdnf protein, rat)
0 (Creb1 protein, rat)

Date Created: 20240108 Date Completed: 20240611 Latest Revision: 20240712

20240713

10.1007/s00210-023-02941-4

38189934