Cannabidiol in the prelimbic cortex modulates the comorbid condition between the chronic neuropathic pain and depression-like behaviour in rats: The role of medial prefrontal cortex 5-HT1A and CB1 receptors

Twenty days after chronic constriction injury (CCI) of the sciatic nerve, there were increases in the mechanical allodynia and the depression-associated behaviours of immobility and mobility in the forced swim (FS). The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is involved in the mechanism of comorbidity between depression and chronic neuropathic pain (NP). Cannabidiol (CBD) treatment in the PrL cortex attenuates both depression-like behaviour and mechanical allodynia in Wistar rats with chronic NP induced by CCI. CBD action into the PrL cortex seems to be due to the activation of mPFC 5HT1A and CB1 receptors. [Display omitted] •PrL cortex seems to play a role in both chronic NP and depression-like behaviours.•The antidepressant effect of CBD may be due to its action in the PrL cortex.•CBD action into the PrL cortex can be due to the activation of CB1 receptors.•CBD action into the PrL cortex can be due to the activation of 5HT1A receptors.•CBD as a potential drug treatment for depressive disorders and chronic NP. The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl2), and the treatment of the PrL cortex with cannabidiol (CBD), the CB1 receptor antagonist AM251 and the 5-HT1A receptor antagonist WAY-100635 were also investigated. Our results showed that CoCl2 decreased the time spent immobile during the FS test but did not alter mechanical allodynia. CBD (at 15, 30 and 60 nmol) in the PrL cortex also decreased the frequency and duration of immobility; however, only the dose of 30 nmol of CBD attenuated mechanical allodynia in rats with chronic NP. AM251 and WAY-100635 in the PrL cortex attenuated the antidepressive and analgesic effect caused by CBD but did not alter the immobility and the mechanical allodynia when administered alone. These data show that the PrL cortex is part of the neural substrate underlying the comorbidity between NP and depression. Also, the previous blockade of CB1 cannabinoid receptors and 5-HT1A serotonergic receptors in the PrL cortex attenuated the antidepressive and analgesics effect of the CBD. They also sugge