Behavioral and c-fos expression changes induced by nitric oxide donors microinjected into the dorsal periaqueductal gray

The dorsolateral periaqueductal gray matter (DLPAG) is a key structure in b ehavioral and autonomic expression of defensive reactions. Inhibitors of ni tric oxide (NO) synthase microinjected into the DLPAG are anxiolytic. The p urpose of the present study was to evaluate the behavioral effects produced by administration of two NO donors, SIN-1 or DEA/NO, into the DLPAG. We al so employed the detection of Fos-like immunoreactivity (FLI) to reveal brai n areas activated by SIN-1 administration. Male Wistar rats (n = 7-11/group ) received intra-DLPAG injection of SIN-1 (150 or 300 nmol), DEA/NO (150, 3 00, or 600 nmol), or saline (0.5 mu l), and their behavior was observed in an open arena during 15 min. For the FLI assay, the animals (n = 3-5/group) were sacrificed 2.25 h after the drug. In a second experiment, rats (n = 5 -7/group) received a first intra-DLPAG injection of saline or methylene blu e (MB, 30 nmol), an NO antagonist, followed by saline or SIN-1 (300 nmol). SIN-1 (300 nmol) induced a flight response characterized by coordinated run ning and oriented jumps with escape attempts. Similar but short-lasting cha nges were seen after the administration of DEA/NO. FLI was dose-dependently induced by SIN-1 in several regions related to defensive reactions, includ ing the periaqueductal gray, hypothalamic nuclei, medial amygdala, and cing ulate cortex (analysis of variance, p < 0.05). A greater number of neurons showing FLI was found ipsilateral to the microinjection site. The drug effe ct was greater at this side in the bed nucleus of the stria terminalis, par aventricular and lateral hypothalamus, cingulate cortex, septohipoccampal n ucleus, and horizontal limb of the diagonal band. The increase in SIN-1-ind uced FLI was attenuated by MB pretreatment in most regions. These results s uggest that NO may participate in the modulation of defensive responses in the DLPAG. (C) 2000 Elsevier Science Inc.