Abstracts

Rationale: We have recently shown that oxytocin (OT) microinjection in amygdala central nucleus (CeA) induced hypergrooming, an experimental model of compulsion in Wistar rats.The Wistar Audiogenic Rat (WAR) strain is an experimental model of epilepsy obtained by the inbreeding of animals genetically susceptible to sound-induced generalized seizures. In the present study, our aim was to evaluate the grooming expression in WAR after OT injection in CeA and to investigate the potential activated circuitry in WAR as compared to Wistar. Methods: WAR and Wistar male rats (270-300 g), all naïve for sound stimuli, were bilaterally cannulated into the CeA. The rats were injected with saline (SAL) or OT and divided into the following 4 groups (strain/drug): WAR/SAL, Wistar/SAL, WAR/OT and Wistar/OT, 5 per group. All groups were videotaped during 1 h, and 90 minutes after injections perfused to perform Fos immunofluorescence to label neuronal activity. OT behavioral effect was evaluated during 1 hour, by means of a grooming score, each five minutes and its statistical significance with a Poisson model. Experimental protocols were in accordance with the Ethics Committee for Animal Experimentation (protocol n° 054/2007). Results: Within the range of 95% of credibility, the groups were compared and the significant findings considering the observation time windows are described below. (1) Grooming frequency was higher in WAR/OT than in WAR/SAL at 20-25, 30-35 and 40-45 minutes, and lower in 35-40 and 55-60. (2) Grooming frequency was higher in Wistar/OT than in Wistar/SAL at 0-35, 40-55 minutes and the opposite at 45-50 minutes. (3) Higher frequencies of grooming were observed in WAR/SAL when compared with Wistar/SAL, during the whole 60 minutes. (4) Grooming frequencies were higher in WAR/OT than in Wistar/OT at 15-35, 40-50 and 55-60 minutes and the opposite at 30-35 minutes. (5) Grooming frequency in WAR/SAL was higher than Wistar/OT at 30-35, 40-45 and 50-55 and the opposite at 35-40, 45-50 and 55-60. (6) Higher frequencies of grooming were observed in WAR/OT when compared to Wistar/SAL during the whole 60 minutes and higher in Wistar/SAL at 10-15, 45-50 and 55-60 minutes. Preliminary data (n=2) showed that OT injected animals (WAR and Wistar), had Fos+ labeling in areas such as orbitofrontal cortex, paraventricular hypothalamic nucleus, striatum, globus pallidus and substantia nigra, among others. Conclusions: Grooming induced by OT microinjection in CeA was exacerbated in WAR, an epileptic strain. Furthermore, WAR strain expresses an enhanced grooming behavior in basal conditions. It will be interesting to evaluate if this endogenous behavioral profile in WAR is related to data from our laboratory showing compulsive grooming induced by OT in the CeA of Wistar rats. The activation of cortico-limbic circuits is associated both with the emergence of seizures and with the occurrence of compulsions. Our data are important for understanding the neurobiology of epilepsy and compulsion co-morbidities. Supported by: FAPESP, Cinapce-FAPESP, PROEX-CAPES, CNPq and FAEPA.