he overarching goal of this dissertation was to assess whether transcutaneous vagus nerve stimulation (tVNS) has beneficial effects over sham stimulation in laboratory models of anxiety.... Show morehe overarching goal of this dissertation was to assess whether transcutaneous vagus nerve stimulation (tVNS) has beneficial effects over sham stimulation in laboratory models of anxiety. Specifically, in Part I, the effects of tVNS were tested in a fear conditioning paradigm to test the utility of tVNS as an add-on treatment for exposure therapy. In Part II, the effects of tVNS as a stand-alone treatment for one of the core symptoms of anxiety – perseverative cognition – was tested within the experimental framework of a Breathing Focus task. Part III deals with working mechanisms: what is the optimal site of the ear to stimulate the auricular branch of the vagus nerve (ABVN) and what is the hypothesized working mechanism underlying the anxiolytic effects of tVNS? Specifically, the effects of tVNS on both physiological as well as behavioral indices of locus coeruleus – noradrenaline (LC-NA) network activity were tested. Show less
Cohn, M.D.; Lith, K. van; Kindt, M.; Pape, L.E.; Doreleijers, T.A.H.; Brink, W. van den; ... ; Popma, A. 2016
Previous studies showed that the mineralocorticoid receptor (MR) is needed for behavioral flexibility in a fear conditioning paradigm. Female mice with forebrain-specific deletion of the MR gene ... Show morePrevious studies showed that the mineralocorticoid receptor (MR) is needed for behavioral flexibility in a fear conditioning paradigm. Female mice with forebrain-specific deletion of the MR gene (MRCaMKCre) were unable to show extinction of contextual fear, and could not discriminate between cue and context fear unlike control mice. In the present study, male and female (MRCaMKCre) mice and control littermates were used to study sex-specific fear conditioning, memory performance and extinction. The fear conditioning paradigm assessed both context- and cue-related fear within one experimental procedure. We observed that at the end of the conditioning all mice acquired the fear-motivated response. During the first minutes of the memory test, both male and female MRCaMKCre mice remembered and feared the context more than the control mice. Furthermore, female MRCaMKCre mice were not able to extinguish this memory even on the second day of memory testing. The female mutants also could not discriminate between cue (more freezing) and context periods (less freezing). In contrast, male MRCaMKCre mice and the controls showed extinction and were capable to discriminate, although the MRCaMKCre mice needed more time before they started extinction. These findings further support the relevance of MR for behavioral flexibility and extinction of fear-motivated behavior. In conclusion, the loss of MR in the forebrain results in large differences in emotional and cognitive behaviors between female and male mice, which suggests a role of this receptor in the female prevalence of stress- and anxiety-regulated disorders. Show less
