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Biological rhythms are synchronized to a 24 h day mostly by the presence of the light-dark cycle. Sudden changes in the timing of the light phase are known to cause disturbances in circadian physiology manifested as internal desynchronization and/or the jet lag syndrome, fatigue and impaired performance after rapid changes of time zones. The occurrence of absence seizures, characterized by reduced consciousness and the presence of 3 - 4 Hz (humans) and 7 - 11 Hz (rats) spikewave discharges (SWD) in EEG, shows daily rhythmic fluctuations. The rhythm of SWD in WAG/Rij rats, a validated, genetic model of absence epilepsy, is generated endogenously by the circadian timing system and shaped by the light-dark cycle, motor activity and a momentary state of vigilance. In constant dim light condition, the rhythmicity in the occurrence of SWD is still present, however, internal desynchronization from the rhythm of motor activity is observed (Smyk et al. 2011). The main goals of the study were to verify the role of the light-dark cycle in the synchronization of the rhythm of SWD in WAG/Rij rats and to deliver evidence for the presence of distinct mechanisms controlling rhythms of SWD and motor activity. Chronic EEG and motor activity recordings were made in adult WAG/Rij rats kept in 12:12 light-dark cycle. After 4 baseline days, the onset of light was delayed by 8 h and the recordings were made during 10 consecutive days. An immediate effect of the phase shift on both rhythms was observed. On the 1st post-shift day the acrophase of the rhythms was advanced of about 7.5 h. After that, it gradually returned to the baseline level, however, the course of the resynchronization of the two rhythms was different. In conclusion, an important role of the light-dark cycle in the resynchronization of the rhythm of absence seizures has been confirmed. The phase shift caused an aggravation of epileptic activity and uncoupling between rhythmic occurrence of SWD and motor activity.
In this study we quantified maternal behavior in genetic epileptic rats with deficiencies in the DA system known to be involved in maternal behavior in order to assess whether these rats have disturbances in maternal care. Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a genetic model for generalized absence epilepsy and Wistar rats were compared. Maternal behavior parameters and activity scores were quantified from post-natal day (PND) 4-6 in an open field in the presence of pups. WAG/Rij rats had less approaches to the pups and higher latencies of approaching them compared to Wistar, while locomotion showed a different pattern over days. This confirms the hypothesis that animals with absence epilepsy show more poor maternal behavior and that these effects cannot be solely attributed to differences in locomotor activity. It is proposed that the reduction in maternal care is attributed to low activity in the mesolimbic DA system.
Haloperidol treatment during pre- and post-natal period affects maternal behavior and this may have long-term effects on the offspring. We examined whether early haloperidol administration to Wistar-Albino-Glaxo dams from Rijswijk (WAG/Rij) and in Wistar control rats would affect maternal care and as a consequence, seizure susceptibility and behavior in the WAG/ Rij's offspring at 3-4 months of age. Nursing dams of this well-validated genetic animal model of absence epilepsy and control dams were injected with haloperidol or saline at PPD 1 to 6. Maternal behavior was evaluated at PPD 7 to 9. Haloperidol-injected WAG/Rij dams showed more pup carryings compared with saline-injected mothers, this effect was not noticed in control Wistar dams. The offspring of haloperidol-treated WAG/Rij dams, tested during adulthood, showed heightened behavioral activity (time spent into the open arms, head dips) in the elevated plus-maze, as well as shorter spike- wave discharges (SWD) as measured in their electroencephalographs activity compared with saline-treated rats. Overall, it can be concluded that deviancies in the DA system as induced by haloperidol facilitates pup carrying/retrieval behavior in WAG/Rij rats and reduces seizure activity of the offspring in adulthood. Therefore, inter-individual differences in seizure properties and behavior in genetically predisposed animals may be due to differences in maternal behavior of the dams.
Anxiety and depression are component of interictal behavioral deteriorations that occur as a consequence of kindling, a procedure to induce chronic epilepsy. The aim of this study was to evaluate the possible effects of electrical stimulation (ES) of paleocerebellar cortex on anxiety and depressive-like behavior in a PTZ kindled epilepsy model. Kindling was induced via pentylenetetrazol (PTZ) (25.0 mg/kg IP daily) during three weeks. Locomotion in open field, elevated plus-maze (EPM) and Porsolt forced swimming test have been used for the assessment of anxiety and depression-like behavior. ES (100 Hz) has been delivered to V-VII lobules of vermal cortex of kindled rats. ES of paleocerebellum reversed kindling-induced reduction of crossings of central squares, increased rearings, and decreased the number of defecations in open field. The duration that kindled animals spent in the open arms of the EPM increased in post- ES period, and the number of enterings into the closed arms of the EPM decreased. The duration of the immobility response in the swimming test in kindled rats was reduced after ESs of paleocerebellum. In all: ES of paleocerebellar structures suppressed anxious and depressive-like behavior in PTZ-kindled rats.
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