Contrasting effects of nitric oxide and corticotropin- releasing factor within the dorsal periaqueductal gray on defensive behavior and nociception in mice

• Published in: Brazilian journal of medical and biological research 2012-04, Vol.45 (4), p.299-307
• Main Authors: Miguel, T T, Gomes, K S, Nunes-de-Souza, R L
• Format: Article
• Language: English
• Subjects: Animals; Antinociception; Anxiety; Behavior, Animal - drug effects; BIOLOGY; Corticotropin-releasing factor; Corticotropin-releasing hormone; Defensive behavior; Glutamic acid receptors; Jumping; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Mesencephalon; Mice; N-Methyl-D-aspartic acid receptors; Nitric oxide; Nitric Oxide - pharmacology; Nitric Oxide Synthase - pharmacology; Nitric-oxide synthase; Nociception - drug effects; Pain perception; Periaqueductal gray; Periaqueductal Gray - drug effects; Periaqueductal Gray - physiology; Periaqueductal gray area; Receptor mechanisms; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Receptors, Corticotropin-Releasing Hormone - drug effects; Receptors, Corticotropin-Releasing Hormone - physiology; Running; Short Communication; Triazenes - pharmacology
• ISSN: 0100-879X; 1414-431X; 1414-431X; 0100-879X
• DOI: 10.1590/S0100-879X2012007500043

The anxiogenic and antinociceptive effects produced by glutamate N-methyl-D-aspartate receptor activation within the dorsal periaqueductal gray (dPAG) matter have been related to nitric oxide (NO) production, since injection of NO synthase (NOS) inhibitors reverses these effects. dPAG corticotropin-releasing factor receptor (CRFr) activation also induces anxiety-like behavior and antinociception, which, in turn, are selectively blocked by local infusion of the CRF type 1 receptor (CRFr1) antagonist, NBI 27914 [5-chloro-4-(N-(cyclopropyl)methyl-N-propylamino)-2-methyl-6-(2,4,6-trichlorophenyl)aminopyridine]. Here, we determined whether i) the blockade of the dPAG by CRFr1 attenuates the anxiogenic/antinociceptive effects induced by local infusion of the NO donor, NOC-9 [6-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine], and ii) the anxiogenic/antinociceptive effects induced by intra-dPAG CRF are prevented by local infusion of N(ω)-propyl-L-arginine (NPLA), a neuronal NOS inhibitor, in mice. Male Swiss mice (12 weeks old, 25-35 g, N = 8-14/group) were stereotaxically implanted with a 7-mm cannula aimed at the dPAG. Intra-dPAG NOC-9 (75 nmol) produced defensive-like behavior (jumping and running) and antinociception (assessed by the formalin test). Both effects were reversed by prior local infusion of NBI 27914 (2 nmol). Conversely, intra-dPAG NPLA (0.4 nmol) did not modify the anxiogenic/antinociceptive effects of CRF (150 pmol). These results suggest that CRFr1 plays an important role in the defensive behavior and antinociception produced by NO within the dPAG. In contrast, the anxiogenic and antinociceptive effects produced by intra-dPAG CRF are not related to NO synthesis in this limbic midbrain structure.