Mice subjected to social isolation (3–4 weeks) exhibit enhanced contextual fear responses and impaired fear extinction. These responses are time-related to a decrease of ... allopregnanolone (Allo) levels in selected neurons of the medial prefrontal cortex, hippocampus, and basolateral amygdala...In socially isolated mice, S-norfluoxetine, in doses that increase brain Allo levels but fail to inhibit serotonin reuptake, greatly attenuates enhanced contextual fear response. The drug SKF decreases corticolimbic Allo levels and enhances the contextual fear response in group housed mice... A recent clinical study reported that cerebrospinal fluid Allo levels also are down-regulated in human PTSD patients and correlate negatively with PTSD symptoms and negative mood. Thus, protracted social isolation of mice combined with tests of fear conditioning may be a suitable model to study emotional behavioral components associated with neurochemical alterations relating to PTSD. Importantly, selective brain steroidogenic stimulants such as S-norfluoxetine, which rapidly increase corticolimbic Allo levels, normalize the exaggerated contextual fear responses resulting from social isolation, suggesting that selective activation of neurosteroidogenesis may be useful in PTSD therapy.
Monday, April 21, 2008
A mouse model for PTSD suggests a therapy
Pibiri et al. have performed experiments on mice that model the emotional hyper-reactivity (including enhanced contextual fear and impaired contextual fear extinction) that is observed in human post traumatic stress disorder (PTSD) patients. They suggest that activation of neuronal steroid synthesis might be useful in PTSD therapy. The edited abstract: