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P.2.a.001 Effect of sesamol pretreatment against lipopolysaccharide-induced depressive and anxiety-like behaviour in Swiss albino mice
S374
P.2.a. Mood disorders and treatment − Affective disorders (basic)
dependence barbiturate sleeping pills, has been shifted to a more acceptable highly benzodiazepines, long-term use at the time of dependence and abuse has become a social problem. This time, suvorexant,receptor antagonist of orexin that control sleep and wakefulness has been launched in Japan. This article reports the usage of three months after the launch in Okehazama Hospital Fujita Kokoro Care Center. Subjects and Method: From December 1, 2014 to February 28, 2015, the patients prescribed suvorexant in our hospital were enrolled in the survey. For the target patient, age, gender, drug name and dosage of prescription drugs, and side effects were investigated from medical records. It should be noted that, with respect to this research to handle personal information carefully, we enough ethical considerations. Results: The subjects enrolled in the study were 21 inpatients (M/F: 9/12) and 22 outpatients (M/F: 5/17), and average age were 54.8 years (15–85 years) and 38.1 years (18– 75 years) respectively. Disease is most often mood disorders (F3) (inpatient/outpatient: 47.6%/44.0%), schizophrenia (inpatient/outpatient: 23.8%/20.0%), anxiety disorders (inpatient/ outpatient: 4.8%/20.0%) it was of the order. Suvorexant before the start of use drugs, was in the order of flunitrazepam > brotizolam > eszopiclone. The frequency of occurrence of side effects less, most common are ones was somnolence. Discussion: From this survey, suvorexant is often found in older inpatients with mood disorder, which it is believed that in view of the patient characteristics and pharmacological agents properties of mid-arousal, and difficulty falling asleep and complaint. In stressful modern society, the brain awake more than necessary, because it might be said that the continued day and night state of the brain, even while you are asleep, more and more people become insomnia caused the failure in arousal system If it is and if, it is presumed that the secretion of orexin are involved. In the future, such as the selection of the subject patient, pharmacist it seems to be necessary to perform an active support towards safer and more appropriate pharmacotherapy. P.1.k.038 Experiences of family caregivers for persons with severe mental illness: an international exploration B. Vermeulen1 ° , H. Lauwers1 , N. Spruytte1 , C. Van Audenhove1 Leuven, LUCAS, Leuven, Belgium
1 KU
Purpose of the study: Family caregivers play a central role in the care for persons with severe mental illness. Following the current mental health reform in developed countries in the direction of more community-based care, expectations toward family caregivers have increased. Survey-based evidence of the experiences of family caregivers exists, but up until now, no comprehensive research has been done [1]. This exploratory study aims to assess the experiences of family caregivers in caring for their relative with severe mental illness. We study aspects related to family caregiver’s (1) sociodemographic characteristics, (2) experiences, (3) satisfaction with professional support and (4) need for additional support. This study was financed by EUFAMI, who received an educational grant from Lundbeck and Otsuka. Methods used: This cross-sectional study was undertaken in 22 countries from 1st June to 31st December 2014. An anonymous self-completion survey was completed by 1111 family caregivers of persons with severe mental illness who were linked with a family caregiver organisation (Australia 26; Austria 49; Belgium
93; Canada 106; Cyprus 2; Denmark 146; Finland 48; France 124; Germany 68; Greece 18; Ireland 53; Israel 10; Italy 46; Malta 52; Netherlands 21; Norway 49; Portugal 11; Russia 48; Spain 59; Sweden 7; Switzerland 4; UK 71). There were no other specific inclusion or exclusion criteria. Summary of results: 1. Characteristics: The average family caregiver is a woman, 58 years of age, caring for a child, for a person with schizophrenia, and for 15 years and 22 hours a week. 2. Experiences: One in three family caregivers feels he or she has reached breaking point, where they feel they cannot carry on with things the way they are. Almost half of family caregivers feel unable to cope with the constant anxiety of caring. 3. Satisfaction with professional support: 39% of family caregivers are dissatisfied with the support received from doctors. 49% of family caregivers are dissatisfied with getting help and support for themselves from professional staff. 35% of family caregivers feel that medical and care staff do not take them seriously. 43% of family caregivers are dissatisfied with their ability to influence important decisions in treatment and care planning. 4. Need for additional support: One out of six family caregivers indicates not being able to take a break from caring. More than 9 out of 10 family caregivers would like additional support to help them in their role as a carer. Conclusion: These results confront policy makers and clinicians with the inadequate recognition of caregivers in mental health care. Therefore, we recommend advancing a paradigm shift that views family caregivers of people with severe mental illness as a resource and a partner [2]. Mental health clinicians need to be aware of evidence-based knowledge of the experiences of family caregivers and the skills required for working inclusively with them. References [1] Caqueo-Ur´ızar, A., Miranda-Castillo, C., Gir´aldez, S., Maturana, S., P´erez, M., Tapia, F., 2014. An updated review on burden on caregivers of schizophrenia patients. Psicothema, 26(2), 235-243. [2] Fleischhacker, W.W., Arango, C., Arteel, P., Barnes, T.R., Carpenter, W., Duckworth, K., Galderisi, L., Halpern, M., Knapp, S.R., Marder, M., Moller, N., Sartorius, P., Woodruff, P., 2014. Schizophrenia—time to commit to policy change. Schizophrenia bulletin 40(Suppl 3), 165-194. Disclosure statement: This study was financed by EUFAMI, who received an educational grant from Lundbeck and Otsuka.
P.2.a. Mood disorders and treatment − Affective disorders (basic) P.2.a.001 Effect of sesamol pretreatment against lipopolysaccharide-induced depressive and anxiety-like behaviour in Swiss albino mice S. Chandra Shaker1 ° , J. Ashok2 , B. Babul Kumar2 , M. Priram3 Institute of Pharmaceutical Education and Research, Pharmacology & Toxicology, India, India; 2 National Institute of Pharmaceutical Education and Research, Pharmacology & Toxicology, Guwahati, India; 3 College of Veterinary Sciences − Assam Agricultural University, Department of Pharmacology, Guwahati, India
1 National
Aim: Sesamol (Sesamum indicum, Linn, Pedaliaceae; 3,4Methylenedioxyphenol) has been used traditionally as a health
P.2.a. Mood disorders and treatment − Affective disorders (basic) supplement in India and worldwide. It is a well-known antioxidant, currently being tried against several neurological disorders. The present study was designed to evaluate the potential of sesamol treatment against lipopolysacharide (LPS)-induced neurobehavioral and neurochemical alterations in Swiss albino mice. Methodology: Sesamol (2, 4, and 8 mg/kg) was administered once daily for 14 consecutive days by oral gavage. On the 14th day, LPS (0.83 mg/kg) was injected (i.p) 30 min after drug administration. The neurobehavioral assessments, forced swim test, tail suspension test, social interaction test, sucrose preference test, open field test, elevatedplusmaze and light-dark box test were conducted 24 h after LPS (0.83 mg/kg) injection. After the behavioral assessment was over, all the animals were sacrificed to collect hippocampus and prefrontal cortex parts. Hippocampus and prefrontal cortex tissue homogenates were made 1:8 using phosphate buffer (Ph 7.4). Protein estimations were carried out for these homogenates. Proinflammatory cytokines (TNF-a, IL1b and IL-6) and antioxidants (reduced glutathione, superoxide dismutase, catalase) were assessed in both hippocampus as well as prefrontal cortex by performing enzyme linked immunosorbant assay (ELISA). In addition neurotrophic factor, BDNF (brain derived neurotrophic factor) was estimated in hippocampal homogenates through western blotting. Results: We found that a single administration of LPS (0.83 mg/kg i.p) significantly (P < 0.05) increased the levels of the proinflammatory cytokines (TNF-a, IL-6, IL-1b) and increased the oxidative stress which is evident by the attenuation of the levels of catalase, SOD and reduced glutathione. In addition, LPS exposure significantly (P < 0.01) increased the immobility time in tail suspension test and forced swim test without affecting spontaneous locomotor activity. Sesamol pretreatment significantly (P < 0.05) ameliorated the anxiety-like behavior as evident from the results of elevated plus maze, light-dark box test and open field test. Sesamol pretreatment also improved the anhedonic behaviour as revealed by sucrose preference test and increased social interaction time. Sesamol (4, and 8 mg/kg) pretreatment also prevented the lipopolysaccharide-evoked depressive-like effect by significantly (P < 0.05) reducing the immobility time in forced swim and tail suspension test. LPS-induced elevated oxidative stress was decreased with sesamol pretreatment due to its potential to increase reduced glutathione concentration, Superoxidedismutase and catalase levels in the hippocampus as well as in the prefrontal cortex. Mangiferin pretreatment also attenuated neuroinflammation significantly (P < 0.01) by reducing the interleukin-1beta, TNF-a and IL-6 levels in hippocampus and prefrontal cortex. Similarly, BDNF levels were significantly declined in LPS treated group, where as in sesamol (4, and 8 mg/kg) treated groups the BDNF levels significantly restored. Conclusion: In conclusion, the data from our experiments demonstrate protective effect of sesamol against LPS-induced depressive and anxiety-like behavior mice. This protective effect is likely due to its inhibition of neuroinflammation, oxidative stress, and prevention of depletion of BDNF level in the mouse brain. Hence, our study suggests that sesamol could be an interesting molecule for targeting neuropsychiatric disorders associated with oxidative stress and neuroinflammation caused by proinflammatory cytokines.
S375
P.2.a.002 Experimental investigation on the effects of some antidepressants on spatial memory performance of old rats E.G. Popa1 , A.C. Cristofor2 , C.E. Lupusoru2 , A.S. Neculai Valeanu3 , E.V. Sindrilar4 , L. Mititelu Tartau2 ° 1 University of Medicine and Pharmacy ‘Gr. T. Popa’ Iasi − Faculty of Pharmacy, Pharmaceutical Technology, Iasi, Romania; 2 university of Medicine and Pharmacy ‘Gr. T. Popa’ Iasi − Faculty of Medicine, Pharmacology-algesiology, Iasi, Romania; 3 university of Agricultural Sciences and Veterinary Medicine, Reproduction, Iasi, Romania; 4 university of Agricultural Sciences and Veterinary Medicine, Surgery, Iasi, Romania Depression is a frequent problem that may affect the elderly persons. Modern treatment of geriatric depression combines pharmacotherapy with alternative methods (psychoterapy, cognitive-behavioural and interpersonal terapies). Pharmacotherapy of depression in elderly patients is based especially on using selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, due to their therapeutic efficacy and favorable side-effect profile [1]. Given the multiple medical conditions and polymedication, but also the pharmacokinetic particularities of elderly patients, the treatment of late-life depression requires a carefully choice of the most convenient antidepressant drugs along with permanent monitoring of their dosage regimen [2]. Purpose: We aimed to investigate the effects of two antidepressant drugs on spontaneous behaviour and cognitive processes in rats (spatial memory). Method: The experiments were carried out on white male Wistar old rats (18 months) distributed into 3 groups of 6 animals each, treated orally (using an eso-gastric device) with a unique daily dose over 1 month period: Group I (Control): saline solution 0.3 ml/100 g weight; Group II (DLX): duloxetine 1.5 mg/kbw; Group III (ESC): escitalopram 2 mg/kbw. The effects of antidepressant drugs on the spontaneous psycho-motor abilities of rats were evaluated using the LE-8811 Actimeter device (PanLab). The effects of antidepressants on spatial memory performance were assessed by recording spontaneous alternation behavior in a single session in the Y-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during an 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed with the following formula: number of alternations divided by total number of arm visits minus 2 [3]. The data were presented as +/− standard deviation and the statistical significance was tested using the ANOVA method implemented in SPSS 17.0 software. P-values less than 0.05 were considered statistically significant compared to those of Control group. Experimental protocol was implemented following the recommendations of the University Committee for Research and Ethical Issues. Results: Both duloxetine and escitalopram administration determined a reduction of rats vertical movements, statistically significant (p < 0.05) compared to Control group in the Actimeter test. The effects of duloxetine were more intense than those of escitalopram. Duloxetine but not escitalopram significantly decreased the number of horizontal movements in the same behavioral model. The oral administration of both antidepressant drugs over one month was associated with an increase of spontaneous alternation rate, statistically significant (p < 0.05) compared to Control group in the Y-maze test. In our experimental conditions the effects of duloxetine were more accentuated than those of escitalopram.
P.2.a. Mood disorders and treatment − Affective disorders (basic)
dependence barbiturate sleeping pills, has been shifted to a more acceptable highly benzodiazepines, long-term use at the time of dependence and abuse has become a social problem. This time, suvorexant,receptor antagonist of orexin that control sleep and wakefulness has been launched in Japan. This article reports the usage of three months after the launch in Okehazama Hospital Fujita Kokoro Care Center. Subjects and Method: From December 1, 2014 to February 28, 2015, the patients prescribed suvorexant in our hospital were enrolled in the survey. For the target patient, age, gender, drug name and dosage of prescription drugs, and side effects were investigated from medical records. It should be noted that, with respect to this research to handle personal information carefully, we enough ethical considerations. Results: The subjects enrolled in the study were 21 inpatients (M/F: 9/12) and 22 outpatients (M/F: 5/17), and average age were 54.8 years (15–85 years) and 38.1 years (18– 75 years) respectively. Disease is most often mood disorders (F3) (inpatient/outpatient: 47.6%/44.0%), schizophrenia (inpatient/outpatient: 23.8%/20.0%), anxiety disorders (inpatient/ outpatient: 4.8%/20.0%) it was of the order. Suvorexant before the start of use drugs, was in the order of flunitrazepam > brotizolam > eszopiclone. The frequency of occurrence of side effects less, most common are ones was somnolence. Discussion: From this survey, suvorexant is often found in older inpatients with mood disorder, which it is believed that in view of the patient characteristics and pharmacological agents properties of mid-arousal, and difficulty falling asleep and complaint. In stressful modern society, the brain awake more than necessary, because it might be said that the continued day and night state of the brain, even while you are asleep, more and more people become insomnia caused the failure in arousal system If it is and if, it is presumed that the secretion of orexin are involved. In the future, such as the selection of the subject patient, pharmacist it seems to be necessary to perform an active support towards safer and more appropriate pharmacotherapy. P.1.k.038 Experiences of family caregivers for persons with severe mental illness: an international exploration B. Vermeulen1 ° , H. Lauwers1 , N. Spruytte1 , C. Van Audenhove1 Leuven, LUCAS, Leuven, Belgium
1 KU
Purpose of the study: Family caregivers play a central role in the care for persons with severe mental illness. Following the current mental health reform in developed countries in the direction of more community-based care, expectations toward family caregivers have increased. Survey-based evidence of the experiences of family caregivers exists, but up until now, no comprehensive research has been done [1]. This exploratory study aims to assess the experiences of family caregivers in caring for their relative with severe mental illness. We study aspects related to family caregiver’s (1) sociodemographic characteristics, (2) experiences, (3) satisfaction with professional support and (4) need for additional support. This study was financed by EUFAMI, who received an educational grant from Lundbeck and Otsuka. Methods used: This cross-sectional study was undertaken in 22 countries from 1st June to 31st December 2014. An anonymous self-completion survey was completed by 1111 family caregivers of persons with severe mental illness who were linked with a family caregiver organisation (Australia 26; Austria 49; Belgium
93; Canada 106; Cyprus 2; Denmark 146; Finland 48; France 124; Germany 68; Greece 18; Ireland 53; Israel 10; Italy 46; Malta 52; Netherlands 21; Norway 49; Portugal 11; Russia 48; Spain 59; Sweden 7; Switzerland 4; UK 71). There were no other specific inclusion or exclusion criteria. Summary of results: 1. Characteristics: The average family caregiver is a woman, 58 years of age, caring for a child, for a person with schizophrenia, and for 15 years and 22 hours a week. 2. Experiences: One in three family caregivers feels he or she has reached breaking point, where they feel they cannot carry on with things the way they are. Almost half of family caregivers feel unable to cope with the constant anxiety of caring. 3. Satisfaction with professional support: 39% of family caregivers are dissatisfied with the support received from doctors. 49% of family caregivers are dissatisfied with getting help and support for themselves from professional staff. 35% of family caregivers feel that medical and care staff do not take them seriously. 43% of family caregivers are dissatisfied with their ability to influence important decisions in treatment and care planning. 4. Need for additional support: One out of six family caregivers indicates not being able to take a break from caring. More than 9 out of 10 family caregivers would like additional support to help them in their role as a carer. Conclusion: These results confront policy makers and clinicians with the inadequate recognition of caregivers in mental health care. Therefore, we recommend advancing a paradigm shift that views family caregivers of people with severe mental illness as a resource and a partner [2]. Mental health clinicians need to be aware of evidence-based knowledge of the experiences of family caregivers and the skills required for working inclusively with them. References [1] Caqueo-Ur´ızar, A., Miranda-Castillo, C., Gir´aldez, S., Maturana, S., P´erez, M., Tapia, F., 2014. An updated review on burden on caregivers of schizophrenia patients. Psicothema, 26(2), 235-243. [2] Fleischhacker, W.W., Arango, C., Arteel, P., Barnes, T.R., Carpenter, W., Duckworth, K., Galderisi, L., Halpern, M., Knapp, S.R., Marder, M., Moller, N., Sartorius, P., Woodruff, P., 2014. Schizophrenia—time to commit to policy change. Schizophrenia bulletin 40(Suppl 3), 165-194. Disclosure statement: This study was financed by EUFAMI, who received an educational grant from Lundbeck and Otsuka.
P.2.a. Mood disorders and treatment − Affective disorders (basic) P.2.a.001 Effect of sesamol pretreatment against lipopolysaccharide-induced depressive and anxiety-like behaviour in Swiss albino mice S. Chandra Shaker1 ° , J. Ashok2 , B. Babul Kumar2 , M. Priram3 Institute of Pharmaceutical Education and Research, Pharmacology & Toxicology, India, India; 2 National Institute of Pharmaceutical Education and Research, Pharmacology & Toxicology, Guwahati, India; 3 College of Veterinary Sciences − Assam Agricultural University, Department of Pharmacology, Guwahati, India
1 National
Aim: Sesamol (Sesamum indicum, Linn, Pedaliaceae; 3,4Methylenedioxyphenol) has been used traditionally as a health
P.2.a. Mood disorders and treatment − Affective disorders (basic) supplement in India and worldwide. It is a well-known antioxidant, currently being tried against several neurological disorders. The present study was designed to evaluate the potential of sesamol treatment against lipopolysacharide (LPS)-induced neurobehavioral and neurochemical alterations in Swiss albino mice. Methodology: Sesamol (2, 4, and 8 mg/kg) was administered once daily for 14 consecutive days by oral gavage. On the 14th day, LPS (0.83 mg/kg) was injected (i.p) 30 min after drug administration. The neurobehavioral assessments, forced swim test, tail suspension test, social interaction test, sucrose preference test, open field test, elevatedplusmaze and light-dark box test were conducted 24 h after LPS (0.83 mg/kg) injection. After the behavioral assessment was over, all the animals were sacrificed to collect hippocampus and prefrontal cortex parts. Hippocampus and prefrontal cortex tissue homogenates were made 1:8 using phosphate buffer (Ph 7.4). Protein estimations were carried out for these homogenates. Proinflammatory cytokines (TNF-a, IL1b and IL-6) and antioxidants (reduced glutathione, superoxide dismutase, catalase) were assessed in both hippocampus as well as prefrontal cortex by performing enzyme linked immunosorbant assay (ELISA). In addition neurotrophic factor, BDNF (brain derived neurotrophic factor) was estimated in hippocampal homogenates through western blotting. Results: We found that a single administration of LPS (0.83 mg/kg i.p) significantly (P < 0.05) increased the levels of the proinflammatory cytokines (TNF-a, IL-6, IL-1b) and increased the oxidative stress which is evident by the attenuation of the levels of catalase, SOD and reduced glutathione. In addition, LPS exposure significantly (P < 0.01) increased the immobility time in tail suspension test and forced swim test without affecting spontaneous locomotor activity. Sesamol pretreatment significantly (P < 0.05) ameliorated the anxiety-like behavior as evident from the results of elevated plus maze, light-dark box test and open field test. Sesamol pretreatment also improved the anhedonic behaviour as revealed by sucrose preference test and increased social interaction time. Sesamol (4, and 8 mg/kg) pretreatment also prevented the lipopolysaccharide-evoked depressive-like effect by significantly (P < 0.05) reducing the immobility time in forced swim and tail suspension test. LPS-induced elevated oxidative stress was decreased with sesamol pretreatment due to its potential to increase reduced glutathione concentration, Superoxidedismutase and catalase levels in the hippocampus as well as in the prefrontal cortex. Mangiferin pretreatment also attenuated neuroinflammation significantly (P < 0.01) by reducing the interleukin-1beta, TNF-a and IL-6 levels in hippocampus and prefrontal cortex. Similarly, BDNF levels were significantly declined in LPS treated group, where as in sesamol (4, and 8 mg/kg) treated groups the BDNF levels significantly restored. Conclusion: In conclusion, the data from our experiments demonstrate protective effect of sesamol against LPS-induced depressive and anxiety-like behavior mice. This protective effect is likely due to its inhibition of neuroinflammation, oxidative stress, and prevention of depletion of BDNF level in the mouse brain. Hence, our study suggests that sesamol could be an interesting molecule for targeting neuropsychiatric disorders associated with oxidative stress and neuroinflammation caused by proinflammatory cytokines.
S375
P.2.a.002 Experimental investigation on the effects of some antidepressants on spatial memory performance of old rats E.G. Popa1 , A.C. Cristofor2 , C.E. Lupusoru2 , A.S. Neculai Valeanu3 , E.V. Sindrilar4 , L. Mititelu Tartau2 ° 1 University of Medicine and Pharmacy ‘Gr. T. Popa’ Iasi − Faculty of Pharmacy, Pharmaceutical Technology, Iasi, Romania; 2 university of Medicine and Pharmacy ‘Gr. T. Popa’ Iasi − Faculty of Medicine, Pharmacology-algesiology, Iasi, Romania; 3 university of Agricultural Sciences and Veterinary Medicine, Reproduction, Iasi, Romania; 4 university of Agricultural Sciences and Veterinary Medicine, Surgery, Iasi, Romania Depression is a frequent problem that may affect the elderly persons. Modern treatment of geriatric depression combines pharmacotherapy with alternative methods (psychoterapy, cognitive-behavioural and interpersonal terapies). Pharmacotherapy of depression in elderly patients is based especially on using selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, due to their therapeutic efficacy and favorable side-effect profile [1]. Given the multiple medical conditions and polymedication, but also the pharmacokinetic particularities of elderly patients, the treatment of late-life depression requires a carefully choice of the most convenient antidepressant drugs along with permanent monitoring of their dosage regimen [2]. Purpose: We aimed to investigate the effects of two antidepressant drugs on spontaneous behaviour and cognitive processes in rats (spatial memory). Method: The experiments were carried out on white male Wistar old rats (18 months) distributed into 3 groups of 6 animals each, treated orally (using an eso-gastric device) with a unique daily dose over 1 month period: Group I (Control): saline solution 0.3 ml/100 g weight; Group II (DLX): duloxetine 1.5 mg/kbw; Group III (ESC): escitalopram 2 mg/kbw. The effects of antidepressant drugs on the spontaneous psycho-motor abilities of rats were evaluated using the LE-8811 Actimeter device (PanLab). The effects of antidepressants on spatial memory performance were assessed by recording spontaneous alternation behavior in a single session in the Y-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during an 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed with the following formula: number of alternations divided by total number of arm visits minus 2 [3]. The data were presented as +/− standard deviation and the statistical significance was tested using the ANOVA method implemented in SPSS 17.0 software. P-values less than 0.05 were considered statistically significant compared to those of Control group. Experimental protocol was implemented following the recommendations of the University Committee for Research and Ethical Issues. Results: Both duloxetine and escitalopram administration determined a reduction of rats vertical movements, statistically significant (p < 0.05) compared to Control group in the Actimeter test. The effects of duloxetine were more intense than those of escitalopram. Duloxetine but not escitalopram significantly decreased the number of horizontal movements in the same behavioral model. The oral administration of both antidepressant drugs over one month was associated with an increase of spontaneous alternation rate, statistically significant (p < 0.05) compared to Control group in the Y-maze test. In our experimental conditions the effects of duloxetine were more accentuated than those of escitalopram.