Flight reactions induced by injection of glutamate N-methyl- d-aspartate receptor agonist into the rat dorsolateral periaqueductal gray are not dependent on endogenous nitric oxide

Abstract

Glutamate N-methyl- d-aspartate (NMDA) receptors and the enzyme neuronal nitric oxide synthase (nNOS) are significantly expressed in the midbrain dorsolateral periaqueductal gray (dlPAG). Local injections of either NMDA-receptor agonists or nitric oxide (NO) donors induce flight reactions in rats. Since the activation of NMDA receptors in the brain increases the synthesis of NO, the present work was conducted to test the hypothesis that the flight reaction induced by intra-dlPAG administration of NMDA would be mediated by endogenous NO. Male Wistar rats with cannulas aimed at the dlPAG received intracerebral injections of l-NAME (NOS inhibitor, 100–200 nmol), carboxy-PTIO (NO scavenger, 1–3 nmol) or ODQ (guanylate cyclase inhibitor, 1–3 nmol). Saline or NMDA (0.1 nmol) was injected 10 min later and the behavioral changes were recorded for 2 min in the injection box. Intra-dlPAG injection of NMDA produced flight reactions characterized by crossings and jumps. Contrary to the initial hypothesis, these effects were not prevented by pretreatment with l-NAME, carboxy-PTIO or ODQ. Although the NO pathway may mediate some effects induced by NMDA receptor activation in the brain, the present results suggest that the administration of NMDA into the dlPAG induces flight reactions by mechanisms that are independent of endogenous NO.