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

Author(s)

Malvestio, R. B. ^{[1, 2]} ; Medeiros, P. ^{[1, 2, 3, 4, 5]} ; Negrini-Ferrari, S. E. ^{[1, 2]} ; Oliveira-Silva, M. ^{[1, 2]} ; Medeiros, A. C. ^{[1, 2, 3, 4, 5]} ; Padovan, C. M. ^{[6, 5]} ; Luongo, L. ^[7] ; Maione, S. ^[7] ; Coimbra, N. C. ^{[1, 4, 5]} ; de Freitas, R. L. ^{[1, 2, 3, 4, 5, 8]}

Affiliation

^[1] Univ S ao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Surg & Anat, Neuroelectrophysiol Multiuser Ctr, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] FMRP USP, Lab Neurosci Pain & Emot, Dept Surg & Anat, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] FMRP USP, Lab Neuroanat & Neuropsychobiol, Dept Pharmacol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Sci & Literature Univ Sao Paulo FFCLRP USP, Ribeirao Preto Sch Philosophy, Dept Psychol, Lab Neurobiol Stress & Depress, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Fed Univ Alfenas UNIFAL MG, Biomed Sci Inst ICB, Str Gabriel Monteiro 700, BR-37130000 Alfenas, MG - Brazil

^[6] Behav Neurosci Inst INeC, Av Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

^[7] IRCCS Neuromed, I-86077 Pozzilli Caserta - Italy

^[8] Uni Campania Luigi Vanvitelli, Div Pharmacol, Dept Expt Med, Naples - Italy

• Document type: Journal article
• Source: Brain Research Bulletin; v. 174, p. 323-338, SEP 2021.
• Web of Science Citations: 1

Abstract

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 suggest that CBD could be a potential medicine for the treatment of depressive and pain symptoms in patients with chronic NP/depression comorbidity. (AU)

• FAPESP's process: 14/16720-5 - Neuromolecular and psychopharmacological investigation on the endovanilloid system and TRPV1 channels of medial prefrontal cortex in mediating chronic neuropathic pain
• Grantee: Mariana de Oliveira Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/25167-2 - Role of glutamatergic, endocannabinoid and endovaniloid systems of medial pre-frontal cortex in neurophatic pain model: Investigation of panic and chronic pain comorbidity
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/13560-5 - Effect of deep brain stimulation and cannabidiol treatment in the subthalamic nucleus on the motors and non-Motors symptoms in the experimental model of Parkinson Disease
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/26228-0 - Psychopharmacological investigation on comorbidity influence between chronic neuropathic pain and depression
• Grantee: Rafael Braghetto Malvestio
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 09/17258-5 - Study of the involvement of nitrergic system and of glutamatergic and cannabinoid-mediated neurotransmission from the medial prefrontal cortex in the analgesia induced by elaborated escape reactions evoked by GABAergic blockade in the medial hypothalamus
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/07902-2 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Young Researchers