Effects of excitatory amino acids and nitric oxide on flight behavior elicited from the dorsolateral periaqueductal gray.
Microinjection of excitatory amino acids (EAA) into the dorsolateral periaqueductal gray (dlPAG) induces flight reactions while EAA antagonists show anxiolytic effects. Part of the effects mediated by NMDA receptors may involve an increase in nitric oxide (NO) production. We showed that nitric oxide synthase (NOS) inhibitors injected into the dlPAG induced anxiolytic effects. Conversely, SIN-1, a NO donor, produced orientated flight reactions that resemble stimulation of the medial hypothalamus. This compound also produced extensive Fos-like immunoreactivity in this region and in other areas related to defensive reactions such as the medial amygdala and cingulate cortex. Since part of the effects of NO involves increases in guanylate cyclase levels, we found that intra-dlPAG injection of 8-Br-cGMP induced a brief flight reaction followed by increased locomotion. In another experiment, we showed that single or repeated restraint stress produced an increased expression of neuronal NOS in the dlPAG and other areas related to defense, as measured by in situ hybridization, diaphorase histochemistry and immunocytochemistry. Together, these data suggest that NO may participate in the modulation of defensive responses in the dlPAG.
De Oliveira
R M
RM
Department of Pharmacology, School of Medicine, FMRP, Campus USP, 14049-900, SP, Ribeirão Preto, Brazil.
Del Bel
E A
EA
Guimarães
F S
FS
D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects*; D018846:Excitatory Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008845:Microinjections; D009473:Neuronal Plasticity / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010487:Periaqueductal Gray / Q000502:physiology*; D051381:Rats
D004791:Enzyme Inhibitors; D018846:Excitatory Amino Acids; D020030:Nitric Oxide Donors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP