Role of glutamate NMDA receptors and nitric oxide located within the periaqueductal gray on defensive behaviors in mice confronted by predator

• Published in: Psychopharmacologia 2009-07, Vol.204 (4), p.617-625
• Main Authors: Carvalho-Netto, Eduardo F., Gomes, Karina S., Amaral, Vanessa C. S., Nunes-de-Souza, Ricardo L.
• Format: Article
• Language: English
• Subjects: Animal behavior; Animals; Arginine - administration & dosage; Arginine - analogs & derivatives; Arginine - pharmacology; Avoidance Learning - physiology; Avoidance Learning - radiation effects; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain; Dose-Response Relationship, Drug; Fear - drug effects; Fear - physiology; Freezing Reaction, Cataleptic - physiology; Fundamental and applied biological sciences. Psychology; Inhibitor drugs; Male; Medical sciences; Mice; N-Methylaspartate - administration & dosage; Neurons; Neurosciences; Neurotransmitters; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type I - metabolism; Original Investigation; Periaqueductal Gray - drug effects; Periaqueductal Gray - metabolism; Pharmacology/Toxicology; Predatory Behavior; Psychiatry; Psychopharmacology; Rats; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate - metabolism; Rodents; Vertebrates: nervous system and sense organs
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-009-1492-9

Rationale The midbrain periaqueductal gray (PAG) is part of the brain system involved in active defense reactions to threatening stimuli. Glutamate N -methyl- d -aspartate (NMDA) receptor activation within the dorsal column of the PAG (dPAG) leads to autonomic and behavioral responses characterized as the fear reaction. Nitric oxide (NO) has been proposed to be a mediator of the aversive action of glutamate, since the activation of NMDA receptors in the brain increases NO synthesis. Objectives We investigated the effects of intra-dPAG infusions of NMDA on defensive behaviors in mice pretreated with a neuronal nitric oxide synthase (nNOS) inhibitor [ N ω-propyl- l -arginine (NPLA)], in the same midbrain site, during a confrontation with a predator in the rat exposure test (RET). Materials and methods Male Swiss mice received intra-dPAG injections of NPLA (0.1 or 0.4 nmol/0.1 μl), and 10 min later, they were infused with NMDA (0.04 nmol/0.1 μl) into the dPAG. After 10 min, each mouse was placed in the RET. Results NMDA treatment enhanced avoidance behavior from the predator and markedly increased freezing behavior. These proaversive effects of NMDA were prevented by prior injection of NPLA. Furthermore, defensive behaviors (e.g., avoidance, risk assessment, freezing) were consistently reduced by the highest dose of NPLA alone, suggesting an intrinsic effect of nitric oxide on defensive behavior in mice exposed to the RET. Conclusions These findings suggest a potential role of glutamate NMDA receptors and NO in the dPAG in the regulation of defensive behaviors in mice during a confrontation with a predator in the RET.