1. 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
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Falconi-Sobrinho LL, Dos Anjos-Garcia T, Hernandes PM, Rodrigues BMP, Almada RC, and Coimbra NC
- Subjects
- Rats, Mice, Male, Animals, Receptors, N-Methyl-D-Aspartate metabolism, Rats, Wistar, Mice, Inbred C57BL, Hypothalamus, Anterior metabolism, Microinjections, Periaqueductal Gray, Nitric Oxide metabolism
- Abstract
Rationale: Previous 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., Objectives: This 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., Methods: First, 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 (CoCl
2 ; 1 mM/0.1 μL) or the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.1 nmol/0.1 μL) on defensive behaviours and antinociception induced by microinjections of SIN-1 in the AH of male C57BL/6 mice., Results: AlexaFluor488-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., Conclusions: These 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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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