Nitric oxide-signalling affects panic-like defensive behaviour and defensive antinociception neuromodulation in the prelimbic cerebral cortex

• Published in: Brain research Vol. 1844; p. 149134
• Main Authors: de Freitas, Renato Leonardo, Acunha, Renata Moreira, Bendaña-Córdoba, Fernando René, Medeiros, Priscila, Melo-Thomas, Liana, Coimbra, Norberto Cysne
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2024
• Subjects: Defensive antinociception; Dorsomedial and ventromedial hypothalamus; Hypothalamic orchestrated escape behaviour; Nitric oxide; Panic-like behaviour; Prelimbic prefrontal cortex; Panic-like behaviour; Nitric oxide; Hypothalamic orchestrated escape behaviour; Defensive antinociception; Prelimbic prefrontal cortex; Dorsomedial and ventromedial hypothalamus
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2024.149134

Effect of microinjection of either NPLA (NOS inhibitor) or c-PTIO (NO scavenger) in the prelimbic division (PrL) of the medial prefrontal cortex (mPFC), followed by microinjection of vehicle or bicuculline methiodide in a concentration of 40 ng/200 nL in the dorsomedial and ventromedial nuclei of the hypothalamus (DMH/VMH) eliciting hypothalamically orchestrated oriented escape behaviour and unconditioned fear-induced antinociception. The activation of the neocortex, diencephalon, and brainstem areas involved in panic-like behaviour and fear-induced antinociception through c-Fos protein activation reveals the neural substrates underlying panic-like responses and defensive antinociception.
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•The GABAergic disinhibition in the medial hypothalamus elicits oriented escape behaviour and defensive antinociception.•Escape behaviour increased c-Fos protein expression in neocortical, diencephalic and mesencephalic structures.•The inhibition of the nNOS in the PrL/mPFC decreased the oriented escape behaviour and defensive antinociception.•The infusion of NO scavenger in the PrL decreased the oriented escape behaviour and defensive antinociception.•Nitric oxide-signalling in the PrL cerebral cortex modulates panic-like reactions and defensive antinociception.
Rationale: The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a key structure in panic. Objectives: To evaluate the role of nitric oxide (NO) in defensive behaviour and antinociception. Methods: Either Nω-propyl-L-arginine (NPLA) or Carboxy-PTIO was microinjected in the PrL cortex, followed by hypothalamic treatment with bicuculline. The exploratory behaviours, defensive reactions and defensive antinociception were recorded. Encephalic c-Fos protein was immunolabelled after escape behaviour. Results: NPLA (an inhibition of nNOs) decreased panic-like responses and innate fear-induced antinociception. The c-PTIO (a membrane-impermeable NO scavenger) decreased the escape behaviour. PrL cortex pre-treatment with c-PTIO at all doses decreased defensive antinociception. c-Fos protein was labelled in neocortical areas, limbic system, and mesencephalic structures. Conclusion: The NPLA and c-PTIO in the PrL/mPFC decreased the escape behaviour and defensive antinociception organised by medial hypothalamic nuclei. The oriented escape behaviour recruits neocortical areas, limbic system, and mesencephalic structures. These findings suggest that the organisation of defensive antinociception recruits NO-signalling mechanisms within the PrL cortex. Furthermore, the present findings also support the role of NO as a retrograde messenger in the PrL cortex during panic-like emotional reactions.