Papers by Victoria Risbrough
AGE, 2010
Evidence suggests that increased glucocorticoid receptor (GR) signaling may contribute to cogniti... more Evidence suggests that increased glucocorticoid receptor (GR) signaling may contribute to cognitive decline with age. We hypothesized that alterations in GR signaling pathway molecules, FK506 binding protein (FKBP) 51 and FKBP52, were associated with memory impairment in aged mice. We used the singletrial object recognition test to measure short-term memory in 18 aged mice compared to 22 young mice, and employed quantitative immunohistochemistry to assess cellular expression of those three proteins in the frontal cortex, hippocampal CA1, and dentate gyrus. Values of the discrimination ratio (DR, a measure of novelty preference) in aged mice were significantly lower than those in young mice (mean 0.54 vs. 0.67, p= 0.003, t test). Aged mice with DR below 0.54 were considered impaired (n=9). In the three neuroanatomic regions studied, the immunoreactivity normalized to the area measured (IRn) for GR was significantly increased in aged mice regardless of their task performance compared to young mice (p<0.005), as was the FKBP52 IRn (p<0.007, U test). In the frontal cortex and CA1, the FKBP51 IRn was significantly lower in impaired aged mice than in unimpaired aged mice (p<0.01 and <0.05, respectively) and in young mice (p<0.05 and <0.01, respectively, Dunn's post hoc test). In aged mice, the frontal cortex FKBP51 IRn correlated directly with DR (r s =0.68, p=0.002, Spearman rank correlation). These observations suggest that recognition memory impairment in aged mice is associated with decreased FKBP51 expression that may promote GR-mediated glucocorticoid signaling to a greater extent than in unimpaired aged mice.
Human Psychopharmacology: Clinical and Experimental, 2012
Objective Heightened anticipation of future events has been characterized as a feature of certain... more Objective Heightened anticipation of future events has been characterized as a feature of certain anxiety disorders. In functional magnetic resonance imaging studies, anticipation of fearful/threatening images has been shown to robustly activate the insular cortex and amygdala in healthy subjects, in subjects with high trait anxiety, and in some with anxiety disorders. Blood oxygenation level dependent activation in response to negative image anticipation is also sensitive to anxiolytic treatment, suggesting that image anticipation probes anxiety systems. It is not clear, however, if behavioral responses to image anticipation are also sensitive to anxiolytics. This study tested the hypothesis that anxiety behaviors during anticipation of negative images are sensitive to anxiolytic treatment. Method This study examined the effects of alprazolam and pregabalin treatment on potentiated startle during affective image anticipation. Results There was an effect of anticipation type (negative versus neutral versus positive) on startle reactivity and subjective ratings, suggesting that the task was effective in assaying negative anticipatory arousal. Both treatments significantly reduced overall startle magnitude. However, neither treatment specifically affected potentiated startle during aversive anticipation. Conclusion These data suggest that potentiated startle in response to anticipation of aversive images is not sensitive to anxiolytic treatments in a healthy population, limiting its use as a predictive model of anxiolytic activity. This article is a US Government work and is in the public domain in the USA.
Uploads
Papers by Victoria Risbrough