Chronic Cannabidiol Treatment Effects on Contextual Fear and Neuropathic Pain in Carioca Rats High and Low Conditioned Freezing.

Generalized anxiety disorder (GAD) and chronic pain often co-occur, and cannabidiol (CBD) has a promising treatment for both conditions. In this study, we evaluated whether chronic systemic treatment with CBD decreases pain sensitivity and anxiety-like behavior in a validated animal model of GAD - the Carioca rat lineages, selectively bred based on extreme responses to contextual fear conditioning: high freezing (CHF), low freezing (CLF), and a non-selected control group (CTL). Male rats from each lineage (n = 32 per group) were submitted to a chronic constriction injury of the sciatic nerve (CCI) or SHAM surgery. Sensory responses were assessed with the von Frey (mechanical sensitivity) and acetone (thermal sensitivity to cold) tests before CCI and on postoperative days 13 and 23. CBD (5mg/kg, i.p., daily) was administered from day 14 to 23. Locomotor and anxiety-like behaviors were evaluated using the open field test (OFT) on day 22, and contextual fear conditioning (CFC) was reassessed on day 24. CBD treatment reduced allodynia across all lineages, although this effect was less in CHF rats. In the OFT, CBD exerted an anxiolytic effect in CTL and CHF rats under CCI, and increased locomotion was observed in CLF+SHAM rats. In the CFC, CBD reduced freezing in all SHAM-treated lineages but not in CHF rats with CCI. BDNF expression in the dorsal hippocampus varied by lineages, with CBD restoring BDNF levels in CTL rats. These findings suggest that CBD has differential analgesic and anxiolytic effects across anxiety-prone and anxiety-resistant rat breeding lineages and may modulate hippocampal plasticity through BDNF. Additionally, these preclinical results can improve future strategies for managing patients with GAD and chronic pain.