Gene-environment interactions have an important role in the development of psychiatric disorders. To generate and validate a new substrain of rats with signs related to schizophrenia, we used selective breeding after postweaning social isolation and chronic ketamine treatment through several generations of animals and compared the subsequent strain to naive rats that were not genetically manipulated. We further investigated whether social isolation and ketamine treatment augmented the appearance of schizophrenic-like signs in these rats. Four experimental groups were studied (n=6-15 rats/group): naive rats without any treatment (NaNo); naive rats with postweaning social isolation and ketamine treatment (NaTr); 15th generation of selectively bred animals without any treatment (SelNo) or selectively bred rats with both isolation and ketamine treatment (SelTr). The startle reaction, tail-flick and novel object recognition tests were used to classify the animals into low- or high-risk for schizophrenia. Reduced pain sensitivity, higher degree of the startle reaction, disturbed prepulse inhibition, altered motor activity and decreased differentiation index in the memory test were observed in the 15th generation of the substrain, along with enhanced grooming behavior. Five functional indices (TF latency, startle reaction, prepulse inhibition, differentiation index, and grooming activity) were rated from 0 to 2, and the analysis of the summarized score revealed that the NaNo group had the lowest overall indication of schizophrenic-like signs, while the SelTr animals scored the highest, suggesting that both heritable and environmental factors were important in the generation of the behavioral alterations. We assume that further breeding after this complex treatment may lead to a valid and reliable animal model of schizophrenia.
Mobile phones have been used to monitor mobility changes during the COVID-19 pandemic but surprisingly few studies addressed in detail the implementation of practical applications involving whole populations. We report a method of generating a “mobility-index” and a “stay-at-home/resting-index” based on aggregated anonymous Call Detail Records of almost all subscribers in Hungary, which tracks all phones, examining their strengths and weaknesses, comparing it with Community Mobility Reports from Google, limited to smartphone data. The impact of policy changes, such as school closures, could be identified with sufficient granularity to capture a rush to shops prior to imposition of restrictions. Anecdotal reports of large scale movement of Hungarians to holiday homes were confirmed. At the national level, our results correlated well with Google mobility data, but there were some differences at weekends and national holidays, which can be explained by methodological differences. Mobile phones offer a means to analyse population movement but there are several technical and privacy issues. Overcoming these, our method is a practical and inexpensive way forward, achieving high levels of accuracy and resolution, especially where uptake of smartphones is modest, although it is not an alternative to smartphone-based solutions used for contact tracing and quarantine monitoring.
Peripherally administered endogenous opioid agonist and NMDA receptor antagonist ligands might be beneficial in inflammatory pain. Because both drugs barely cross the blood-brain barrier, their local administration causes no central side effects.
The validation of the translational utility of this new rat substrain by electrophysiological investigations revealed that these rats show abnormalities that may model a part of the neurophysiological deficits observed in schizophrenia.
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