- Email: [email protected]
013 — (CEC0090) Experimental characterization of antidyskinetic and promnestic effects of donepezil in old mice
186
Abstracts
while in the mPFC, the potency remained similar to basal levels. In postictal segments, the power in LG and HG frequencies decreased compared with baseline, while the power in HFOs increased in both analyzed regions. Delta postictal segment presented opposite activities in the mPFC and hippocampus, with sustained increase in the mPFC and no difference from baseline in the hippocampus. Discussion/conclusions: Using the present TLE model, we were able to induce late SRSs in an interval of 75 days, which had the EEG onset predominantly in the hippocampus and later spread to the cortex. Our results show electrographic changes in the preictal and postictal segments in all analyzed oscillations in the mPFC and at high frequencies in the hippocampus. Changes in theta and HG frequency bands have been associated with cognitive deficits and psychiatric disorders, and an important relationship between changes in HFOs and the process of epileptogenesis has been suggested. The next steps will be the characterization of electrophysiological patterns in association with behavioral alterations generally found in the interictal period. This analysis will possibly provide relevant information about which energy band spectral in these conditions could predict SRSs and/or cognitive deficits. Acknowledgments/financial support: FAPESP, no.: 2011/10898-9. doi:10.1016/j.yebeh.2014.08.044
012 — (CAM0047) Previous aerobic exercise program does not alter seizure susceptibility in adult female rats D.V. Campos, A.A. Almeida, R.M. Arida, L.G.Z. Baliego, E.A. Cavalheiro, J. Fernandes, S. Gomes da Silva, G.M. Lopim, A.F. Maia, D.A. Scerni, F.A. Scorza UNIFESP, Brazil Rationale: Although recent studies have shown the importance of physical activity on seizure frequency and severity in both men and male animals with epilepsy, this effect in women and female rats remains unexplored. The female contingent deserves special attention because of the hormonal alterations related to the estrous cycle. Endocrine and reproductive alterations are frequently reported to occur in women with temporal lobe epilepsy as well as in female rats in different experimental models of limbic seizures. Several studies have suggested an association between seizure susceptibility and estrogen/ progesterone ratio, showing a decreased number of seizures during the luteal phase, when progesterone concentration is highest. Besides, several authors have observed a high frequency of anovulatory cycles or inadequate luteal phase in women with epilepsy. Considering the reported data about the influence of physical activity programs over the epileptogenic process and epilepsy, we aimed to assess whether an aerobic physical activity program may alter seizure susceptibility to subsequent pilocarpine insult. Methods: This study used forty adult female Wistar rats divided into 2 groups: exercised rats (EXs) and control rats (CTLs). The animals of the EX group were submitted daily to 20 sessions of aerobic exercise on the treadmill at 18 m/min for 30 min. After the final exercise session, all the animals underwent a pilocarpine injection (360 mg/kg), and latency for the first motor symptoms, number of animals that developed status epilepticus (SE), intensity of motor symptoms, and the latency to reach SE were assessed. The estrous cycle phases of all animals were monitored daily at the beginning of the exercise program until the pilocarpine injection. Results: The results showed no significant differences between the groups to any of the analyzed parameters (latency of first motor symptoms (min): CTLs: 3.53 ± 1.64 and EXs: 3.25 ± 1.77; intensity of motor symptoms (based on Racine's scale): CTLs: 11.05 ± 6.70 and EXs:
18.6 ± 15.06; latency to reach SE (min): CTLs: 26.8 ± 12.2 and EXs: 26.29 ± 9.38; and number of animals that developed SE: CTLs: 12 and EXs: 14). Discussion/conclusions: These data show that a previous aerobic exercise program does not alter the behavioral response after a pilocarpine injection, at least in adult female rats. However, further investigation is needed to evaluate whether the epileptogenic process is affected or not by a previous physical activity program. Acknowledgments/financial support: CAPES, CNPq, FAPESP, and INNT. doi:10.1016/j.yebeh.2014.08.045
013 — (CEC0090) Experimental characterization of antidyskinetic and promnestic effects of donepezil in old mice L.M.B. Ceccona,b, R. Frussa-Filhob, A.W. Hollaisb, L.B. Lopes-Silvac, C.L. Pattic, L.T.C. Ribeirob, R. Santosb, F. Talhatib, K.A. Zaninc a UNIFESP, Brazil b Departamento de Farmacologia, UNIFESP, Brazil c Departamento de Psicobiologia, UNIFESP, Brazil Rationale: Oral dyskinesia (OD), the most serious iatrogenic movement disorder, is developed because of pharmacological treatments or as a spontaneous syndrome. The occurrence of spontaneous OD in elderly people who had never undergone treatment with neuroleptics has been frequently reported. It has been reported that the hyperkinetic movements associated with OD can reflect a dopaminergic–cholinergic imbalance due to either a dopaminergic hyperfunction or a cholinergic hypofunction. In the same way, a myriad of experimental data report the role of cholinergic dysfunction in age-related memory deficits. The aim of this study was to investigate the effects of acute administration of donepezil, an acetylcholinesterase inhibitor agent, on spontaneous orofacial movements and on memory deficits in old mice. Methods: Old (18 to 24 months) or three-month-old (adult, Adu) mice were acutely treated with saline (S) and donepezil (Don) at doses 1, 2, or 3 mg/kg and, 30 min later, had their spontaneous vacuous chewing movement frequencies evaluated. Then, mice were submitted to the plus-maze discriminative avoidance task (PM-DAT). This animal model concomitantly evaluates learning and retention of discriminative avoidance task as well as anxiety-like behavior and motor activity. In this animal model, the aversive stimuli consisted of a 100-W light and blowing air produced by a 110-V hairdryer positioned over the aversive enclosed arm. The aversive stimuli were present during the 10-min training session. Test sessions lasted 3 min, performed in the absence of the aversive stimuli. Results: Our results showed that the highest doses of donepezil (2 or 3 mg/kg) abolished the expression of spontaneous oral dyskinesia in old mice. As expected, there were no basal significant differences on animal behavior during the training session when learning, anxiety, and motor activity were evaluated. In the test session, only old mice treated with Don (2 mg/kg) were able to discriminate the aversive enclosed arm from the nonaversive one, showing memory retention. There were no differences on either percent time spent in the open arms or total number of entries. Discussion/conclusions: Our findings suggest that pretraining donepezil administration can improve the memory retention and also abolish the spontaneous orofacial movements in senile mice. Acknowledgments/financial support: FAPESP, AFIP, CNPq, and CAPES. doi:10.1016/j.yebeh.2014.08.046
Abstracts
while in the mPFC, the potency remained similar to basal levels. In postictal segments, the power in LG and HG frequencies decreased compared with baseline, while the power in HFOs increased in both analyzed regions. Delta postictal segment presented opposite activities in the mPFC and hippocampus, with sustained increase in the mPFC and no difference from baseline in the hippocampus. Discussion/conclusions: Using the present TLE model, we were able to induce late SRSs in an interval of 75 days, which had the EEG onset predominantly in the hippocampus and later spread to the cortex. Our results show electrographic changes in the preictal and postictal segments in all analyzed oscillations in the mPFC and at high frequencies in the hippocampus. Changes in theta and HG frequency bands have been associated with cognitive deficits and psychiatric disorders, and an important relationship between changes in HFOs and the process of epileptogenesis has been suggested. The next steps will be the characterization of electrophysiological patterns in association with behavioral alterations generally found in the interictal period. This analysis will possibly provide relevant information about which energy band spectral in these conditions could predict SRSs and/or cognitive deficits. Acknowledgments/financial support: FAPESP, no.: 2011/10898-9. doi:10.1016/j.yebeh.2014.08.044
012 — (CAM0047) Previous aerobic exercise program does not alter seizure susceptibility in adult female rats D.V. Campos, A.A. Almeida, R.M. Arida, L.G.Z. Baliego, E.A. Cavalheiro, J. Fernandes, S. Gomes da Silva, G.M. Lopim, A.F. Maia, D.A. Scerni, F.A. Scorza UNIFESP, Brazil Rationale: Although recent studies have shown the importance of physical activity on seizure frequency and severity in both men and male animals with epilepsy, this effect in women and female rats remains unexplored. The female contingent deserves special attention because of the hormonal alterations related to the estrous cycle. Endocrine and reproductive alterations are frequently reported to occur in women with temporal lobe epilepsy as well as in female rats in different experimental models of limbic seizures. Several studies have suggested an association between seizure susceptibility and estrogen/ progesterone ratio, showing a decreased number of seizures during the luteal phase, when progesterone concentration is highest. Besides, several authors have observed a high frequency of anovulatory cycles or inadequate luteal phase in women with epilepsy. Considering the reported data about the influence of physical activity programs over the epileptogenic process and epilepsy, we aimed to assess whether an aerobic physical activity program may alter seizure susceptibility to subsequent pilocarpine insult. Methods: This study used forty adult female Wistar rats divided into 2 groups: exercised rats (EXs) and control rats (CTLs). The animals of the EX group were submitted daily to 20 sessions of aerobic exercise on the treadmill at 18 m/min for 30 min. After the final exercise session, all the animals underwent a pilocarpine injection (360 mg/kg), and latency for the first motor symptoms, number of animals that developed status epilepticus (SE), intensity of motor symptoms, and the latency to reach SE were assessed. The estrous cycle phases of all animals were monitored daily at the beginning of the exercise program until the pilocarpine injection. Results: The results showed no significant differences between the groups to any of the analyzed parameters (latency of first motor symptoms (min): CTLs: 3.53 ± 1.64 and EXs: 3.25 ± 1.77; intensity of motor symptoms (based on Racine's scale): CTLs: 11.05 ± 6.70 and EXs:
18.6 ± 15.06; latency to reach SE (min): CTLs: 26.8 ± 12.2 and EXs: 26.29 ± 9.38; and number of animals that developed SE: CTLs: 12 and EXs: 14). Discussion/conclusions: These data show that a previous aerobic exercise program does not alter the behavioral response after a pilocarpine injection, at least in adult female rats. However, further investigation is needed to evaluate whether the epileptogenic process is affected or not by a previous physical activity program. Acknowledgments/financial support: CAPES, CNPq, FAPESP, and INNT. doi:10.1016/j.yebeh.2014.08.045
013 — (CEC0090) Experimental characterization of antidyskinetic and promnestic effects of donepezil in old mice L.M.B. Ceccona,b, R. Frussa-Filhob, A.W. Hollaisb, L.B. Lopes-Silvac, C.L. Pattic, L.T.C. Ribeirob, R. Santosb, F. Talhatib, K.A. Zaninc a UNIFESP, Brazil b Departamento de Farmacologia, UNIFESP, Brazil c Departamento de Psicobiologia, UNIFESP, Brazil Rationale: Oral dyskinesia (OD), the most serious iatrogenic movement disorder, is developed because of pharmacological treatments or as a spontaneous syndrome. The occurrence of spontaneous OD in elderly people who had never undergone treatment with neuroleptics has been frequently reported. It has been reported that the hyperkinetic movements associated with OD can reflect a dopaminergic–cholinergic imbalance due to either a dopaminergic hyperfunction or a cholinergic hypofunction. In the same way, a myriad of experimental data report the role of cholinergic dysfunction in age-related memory deficits. The aim of this study was to investigate the effects of acute administration of donepezil, an acetylcholinesterase inhibitor agent, on spontaneous orofacial movements and on memory deficits in old mice. Methods: Old (18 to 24 months) or three-month-old (adult, Adu) mice were acutely treated with saline (S) and donepezil (Don) at doses 1, 2, or 3 mg/kg and, 30 min later, had their spontaneous vacuous chewing movement frequencies evaluated. Then, mice were submitted to the plus-maze discriminative avoidance task (PM-DAT). This animal model concomitantly evaluates learning and retention of discriminative avoidance task as well as anxiety-like behavior and motor activity. In this animal model, the aversive stimuli consisted of a 100-W light and blowing air produced by a 110-V hairdryer positioned over the aversive enclosed arm. The aversive stimuli were present during the 10-min training session. Test sessions lasted 3 min, performed in the absence of the aversive stimuli. Results: Our results showed that the highest doses of donepezil (2 or 3 mg/kg) abolished the expression of spontaneous oral dyskinesia in old mice. As expected, there were no basal significant differences on animal behavior during the training session when learning, anxiety, and motor activity were evaluated. In the test session, only old mice treated with Don (2 mg/kg) were able to discriminate the aversive enclosed arm from the nonaversive one, showing memory retention. There were no differences on either percent time spent in the open arms or total number of entries. Discussion/conclusions: Our findings suggest that pretraining donepezil administration can improve the memory retention and also abolish the spontaneous orofacial movements in senile mice. Acknowledgments/financial support: FAPESP, AFIP, CNPq, and CAPES. doi:10.1016/j.yebeh.2014.08.046