Effects of the SARM ACP-105 on rotorod performance and cued fear conditioning in sham-irradiated and irradiated female mice

Brain Res. 2011 Mar 24;1381:134-40. doi: 10.1016/j.brainres.2010.12.088. Epub 2011 Jan 8.

Abstract

Female mice are more susceptible to radiation-induced cognitive changes than male mice. Previously, we showed that, in female mice, androgens antagonize age-related cognitive decline in aged wild-type mice and androgens and selective androgen receptor modulators (SARMs) antagonize cognitive changes induced by human apolipoprotein E4, a risk factor for developing age-related cognitive decline. In this study, the potential effects of the SARM ACP-105 were assessed in female mice that were either sham-irradiated or irradiated with ¹³⁷Cesium at a dose of 10Gy. Behavioral testing started 2 weeks following irradiation. Irradiation impaired sensorimotor function in vehicle-treated mice but not in ACP-105-treated mice. Irradiation impaired cued fear conditioning and ACP-105 enhanced fear conditioning in sham-irradiated and irradiated mice. When immunoreactivity for microtubule-associated protein 2 was assessed in the cortex of sham-irradiated mice, there was a brain area × ACP-105 interaction. While ACP-105 reduced MAP-2 immunoreactivity in the sensorimotor cortex, there was a trend towards increased MAP-2 immunoreactivity in the enthorhinal cortex. No effect on MAP-2 immunoreactivity was seen in the irradiated cortex or sham-irradiated or irradiated hippocampus. Thus, there are relatively early radiation-induced behavioral changes in female mice and reduced MAP-2 levels in the sensorimotor cortex following ACP-105 treatment might contribute to enhanced rotorod performance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Azabicyclo Compounds / pharmacology*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / radiation effects
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / radiation effects
  • Fear / drug effects*
  • Fear / radiation effects
  • Female
  • Immunohistochemistry
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Motor Activity / drug effects*
  • Motor Activity / radiation effects
  • Rotarod Performance Test
  • Synaptophysin / metabolism

Substances

  • 2-chloro-4-(3-hydroxy-3-methyl-8-azabicyclo(3.2.1)oct-8-yl)-3-methylbenzonitrile
  • Azabicyclo Compounds
  • Microtubule-Associated Proteins
  • Synaptophysin