Fos-like immunoreactivity in central nervous system of mice simultaneously exposed to the elevated plus-maze and nociception

Abstract

It has been demonstrated that mice exhibit antinociception when they are exposed to the elevated plus-maze (EPM), an animal model of anxiety. To investigate which brain structures are activated during EPM exposure, the present study assessed the immunohistochemical staining for Fos-like immunoreactivity (Fos-LI) in mice intraperitoneally injected with saline or 0.6% acetic acid (which produces nociception) and confined in the open arm (threatening situation) or enclosed arm (control) of the EPM. The following structures were investigated: magnus, dorsal and median raphe nuclei (MR, DR and MnR), periaqueductal gray matter (PAG), dorsal and ventral hippocampus (DH and VH), amygdala (AMY), hypothalamus (HYP) and superior and inferior colliculi (SC and IC). After four days of habituation (habituation was conducted by handling the animals daily for a period of 10 minutes followed by i.p. injection of saline 0.1 mL/10 g), mice received i.p. injection of 0.6% acetic acid or saline and were confined in open or enclosed arms of the EPM. Results showed that open arm confinement increased the number of positive cells for Fos in MnR, PAG and IC, indicating that the fear produced by the threat of the open arms is modulated by these structures. Although statistical analyses did not reveal any effect for nociception factor, (i.e. no effect of acetic acid) the increase in Fos expression was recorded only in animals treated with i.p. acetic acid, suggesting that the simultaneous presence of nociception could be related to an enhanced recruitment of neurons in those midbrains structures.