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bioRxiv · 10.1101/638452

Oxytocin, Compulsion and Epilepsy: Insights from a Complex Behavioral and Neuronal Networks Association

Marroni, S.·Rodrigues Santos, V.·Castro, O. W.·Tejada, J.·Santos, J. C.·Cortes de Oliveira, J. A.·Garcia-Cairasco, N.
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Abstract

Previously we have demonstrated that microinjection of oxytocin (OT) into the central nucleus of amygdala (CeA) induces hypergrooming in Wistar rats, a model of compulsion. The Wistar Audiogenic Rat (WAR) strain is a genetic model of generalized tonic-clonic seizures. Here we quantified grooming behavior in WAR, with grooming scores, flowcharts and directed graphs of syntactic and non-syntactic grooming chains, after bilateral administration of OT or saline (SAL) into the CeA and investigated the association between hypergrooming and imunohistochemistry of Fos activated compulsion networks and proposing a computational model of grooming behavior. The activated networks, driven from a CeA OT-dependent grooming pattern, in both Wistar and WAR were detected as Fos+ regions: orbitofrontal cortex, striatum, paraventricular nucleus of the hypothalamus, dentate gyrus, substantia nigra compacta and reticulata. In conclusion we can drive hypergrooming in WARs, defined previously as a model of ritualistic motor behavior in Wistar rats, with OT from CeA, a limbic structure and one of the principal amygdala complex outputs. Furthermore, our current pioneer behavioral and cellular description considers that hypergrooming (compulsion) in WARs is a comorbidity because: (1) WARs have the highest grooming scores, when exposed only to novelty (2) WARs have better grooming scores than Wistars after CeA-SAL, (3) WARs perform much better than Wistars in OT-CeA-dependent highly stereotyped behavioral sequences, detected by flowcharts as a combination of syntactic/non-syntactic grooming chains, (4) the behavioral sequences here demonstrated for grooming and hypergrooming can be modeled as quite reliable Markov chains and (5) with the exception of CeA-SAL injected animals, an exquisite map of brain Fos expression was detected in typical cortico-striatal-thalamic-basal ganglia-cortical circuit, among new areas, driven by OT-CeA.\n\nAuthor SummaryGrooming is a complex set of regular behavioral sequences in rodents that can be mimicked with several pharmacological or molecular biology interventions. We have demonstrated previously that microinjection of the brain peptide oxytocin into the amygdala, a limbic region, induces hypergrooming in Wistar rats, a model of compulsion. The Wistar Audiogenic Rat strain is a genetic model of generalized seizures, in fact a model of epilepsy. Here we quantified grooming behavior in Wistar Audiogenic Rats, using several behavioral tools such as grooming scores, behavioral sequences and graphs of grooming chains, after bilateral administration of the oxytocin or its control (saline) into the amygdala. We also investigated the association between hypergrooming and activation of compulsion networks, proposing a computational (virtual) model of grooming behavior. Basically we were able to detect activated networks, driven from amygdala and the consequent oxytocin-dependent grooming pattern in epileptic and control animals. Those circuits are composed of cortical and subcortical areas, usually associated to the expression of motor rituals or compulsions. In conclusion, we can drive hypergrooming in epileptic animals, as compared to the previously defined model of ritualistic/compulsive motor behavior in control, rats. We concluded that hypergrooming (compulsion) is endogenously present in epileptic animals as a co-existent event (comorbidity), because when they were exposed to novelty, they express better grooming scores than control animals. The behavioral sequences here demonstrated for grooming and hypergrooming can be simulated as chains, where associations can be predicted from probabilities. Finally, an exquisite map of brain-activated cells was detected in both epileptic animal and their controls, in typical cortico-subcortical structures associated with rituals, but driven from a region which control emotions.

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Marroni, S., Rodrigues Santos, V., Castro, O. W., Tejada, J., Santos, J. C., Cortes de Oliveira, J. A., Garcia-Cairasco, N.. 2019-05-14. Oxytocin, Compulsion and Epilepsy: Insights from a Complex Behavioral and Neuronal Networks Association. https://doi.org/10.1101/638452

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