Cannabidiol in the dorsal hippocampus attenuates emotional and cognitive impairments related to neuropathic pain: role of prelimbic neocortex-hippocampal connections
Author:
Medeiros Ana Carolina1, Medeiros Priscila2, Pigatto Glauce Regina3, Coimbra Norberto Cysne3, de Freitas Renato Leonardo1ORCID
Affiliation:
1. Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto (SP), 14049-900, Brazil. 2. Department of General and Specialized Nursing, Ribeirão Preto Nursing School of the University of São Paulo (EERP-USP) Av. Bandeirantes, 3900, Ribeirão Preto (SP), 14049-900, Brazil. 3. Department of Pharmacology, FMRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto (SP), 14049-900, Brazil.
Abstract
Abstract
Background and Purpose
Chronic neuropathic pain (NP) is commonly associated with cognitive and emotional impairments. Cannabidiol (CBD) presents a broad spectrum of action with a potential analgesic effect. This work investigates the CBD effect on comorbidity between chronic NP, depression, and memory impairment.
Experimental Approach
The connection between the neocortex and the hippocampus was investigated with biotinylated dextran amine (BDA) deposits in the prelimbic cortex (PrL). Wistar rats were submitted to chronic constriction injury (CCI) of the sciatic nerve and CA1-treatment with CBD (15, 30, 60 nmol).
Key Results
BDA-labeled were found in CA1 and dentate gyrus. CCI-induced mechanical and cold allodynia increased c-Fos protein expression in the PrL and CA1. The number of astrocytes in PrL and CA1 increased, and the number of neuroblasts decreased in CA1. The CCI animals showed increasing depressive-like behaviors, such as memory impairment. CBD (60 nmol) treatment decreased mechanical and cold allodynia, attenuated depressive-associated behaviors, and improved memory performance. Cobalt chloride (CoCl2: 1 nM), WAY-100635 (0.37 nmol), and AM251 (100 nmol) intra-PrL reversed the CBD (60 nmol) effect intra-CA1, both in nociceptive, cognitive, and depressive behaviors.
Conclusion
CBD represents a promising therapeutic perspective in the pharmacological treatment of chronic NP and associated comorbidities such as depression and memory impairments. The CBD effects possibly recruit the CA1-PrL pathway, inducing neuroplasticity. CBD acute treatment into the PrL cortex produces functional, molecular, and morphological improvements.
Publisher
Research Square Platform LLC
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