Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic-like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice

Author(s)

Falconi-Sobrinho, Luiz Luciano ; dos Anjos-Garcia, Tayllon ; Hernandes, Paloma Molina ; Rodrigues, Bruno Mangili de Paula ; Almada, Rafael Carvalho ; Coimbra, Norberto Cysne

• Document type: Journal article
• Source: Psychopharmacology; v. N/A, p. 17-pg., 2023-01-17.

Abstract

RationalePrevious studies suggested that the dorsal column of the periaqueductal grey matter (dPAG) can be a target of neural pathways from hypothalamic nuclei involved in triggering fear-related defensive responses. In turn, evidence is provided suggesting that microinjection of the nitric oxide (NO) donor SIN-1 into the anterior hypothalamus (AH) of mice evokes panic-like behaviours and fear-induced antinociception. However, it is unknown whether the dPAG of mice mediates these latter defensive responses organised by AH neurons.ObjectivesThis study was designed to examine the role of dPAG in mediating SIN-1-evoked fear-induced defensive behavioural and antinociceptive responses organised in the AH of mice.MethodsFirst, neural tract tracing was performed to characterise the AH-dPAG pathways. Then, using neuropharmacological approaches, we evaluated the effects of dPAG pretreatment with either the non-selective synaptic blocker cobalt chloride (CoCl2; 1 mM/0.1 mu L) or the competitive N-methyl-d-aspartate (NMDA) receptor antagonist LY235959 (0.1 nmol/0.1 mu L) on defensive behaviours and antinociception induced by microinjections of SIN-1 in the AH of male C57BL/6 mice.ResultsAlexaFluor488-conjugated dextran-labelled axonal fibres from AH neurons were identified in both dorsomedial and dorsolateral PAG columns. Furthermore, we showed that pre-treatment of the dPAG with either CoCl2 or LY235959 inhibited freezing and impaired oriented escape and antinociception induced by infusions of SIN-1 into the AH.ConclusionsThese findings suggest that the panic-like freezing and oriented escape defensive behaviours, and fear-induced antinociception elicited by intra-AH microinjections of SIN-1 depend on the activation of dPAG NMDA receptors. (AU)

• FAPESP's process: 17/22647-7 - Study of glutamatergic pathways from the medial amygdala on ventromedial hypothalamus endocannabinoid signalling during the defensive behaviour elicited by mice threatened by venomous snakes
• Grantee: Tayllon dos Anjos Garcia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/22681-7 - Involvement of Opioid and Endocanabinoid Receptors of the Substantia Nigra, Pars Reticulata, in the Modulation of the Activity of Nigro-Tectal GABAergic Pathways during the Organization of Defensive Behaviour of Mice Confronted with Venomous Snakes
• Grantee: Rafael Carvalho Almada
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/11855-8 - Study of corpus striatum and ventral mesencephalon endocanabinoid influence on neostriato-nigro-tectal GABAergic pathways during panic reactions of rodents threatened by venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 07/01174-1 - Study of the Involvement of opioid-, serotonergic- and noradrenergic-mechanisms of the pain endogenous inhibitory system in antinociceptive processes induced by oriented escape reactions evoked by chemical stimulation of the merdial hypothalamus
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/01713-7 - Fear and anxiety: role of orexinergic system in the prefrontal cortex
• Grantee: Rafael Carvalho Almada
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 18/03898-1 - Fear and anxiety: role of the orexinergic system in the medial prefrontal cortex
• Grantee: Rafael Carvalho Almada
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/10984-8 - Influence of the anterior cingulate cortex and involvement of hypothalamic NMDA and AMPA/kainite glutamatergic receptorsin the organization of the defensive behaviorand innate fear-induced antinociception elaborated by posterior hypothalamus
• Grantee: Luiz Luciano Falconi Sobrinho
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/15050-7 - Study of the role played by endocannabinoid and endovaniloid signalling in the pallidum on the activity of the neostriatum-pallido-nigral disinhibitory and nigro-tectal inhibitory pathways during the organization of innate fear of animals confronted to snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants