Systemic Chronic Treatment with Cannabidiol in Carioca High- and Low-Conditioned Freezing Rats in the Neuropathic Pain Model: Evaluation of Pain Sensitivity.

Studies have shown high comorbidity of anxiety disorder and chronic pain; generalized anxiety disorder (GAD) and neuropathic pain are among these pathologies. Cannabidiol (CBD) has been considered a promising treatment for these conditions. This study investigated whether chronic systemic treatment with CBD alters pain in high- (CHF) and low-freezing (CLF) Carioca rats (GAD model) and control rats (CTL) submitted to chronic neuropathic pain. The rats were evaluated in the sensory aspects (von Frey, acetone, and hot plate tests) before the chronic constriction injury of the ischiatic nerve (CCI) or not (SHAM) and on days 13 and 23 after surgery. Chronic treatment with CBD (5 mg/kg daily) was used for ten days, starting the 14th day after surgery. The open field test on the 22nd also evaluated locomotion and anxiety-like behavior. CBD treatment had an anti-allodynic effect on the mechanical and thermal threshold in all lineages; however, these effects were lower in the CHF and CLF lineages. Considering emotional evaluation, we observed an anxiolytic effect in CTL+CCI and CHF+CCI after CBD treatment and increased mobility in CLF+SHAM rats. These results suggest that the CBD mechanical anti-allodynic and emotional effects can depend on anxiety level.

Cued Fear Conditioning in Carioca High- and Low-Conditioned Freezing Rats.

Anxiety disorders (AD) comprise a broad range of psychiatric conditions, including general anxiety (GAD) and specific phobias. For the last decades, the use of animal models of anxiety has offered important insights into the understanding of the association between these psychopathologies. Here, we investigate whether Carioca high- and low-conditioned freezing rats (CHF and CLF, respectively), a GAD animal model of anxiety, show similar high- and low-freezing behavioral phenotypes for cued auditory fear conditioning. Adult CHF (n = 16), CLF (n = 16) and normal age-matched Wistar rats (control, CTL, n = 16) were tested in a classical auditory-cued fear conditioning paradigm over 3 days (Tone + Shock and Tone only groups, n = 8 per treatment). Freezing responses were measured and used as evidence of fear conditioning. Overall, both CHF and CLF rats, as well as CTL animals displayed fear conditioning to the auditory CS. However, CLF animals showed a rapid extinction to the auditory conditioned stimulus compared to CHF and CTL rats. We discuss these findings in the context of the behavioral and neuronal differences observed in rodent lines of high and low anxiety traits.