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P.4.04 Interaction between CRF and noradrenergic system in the rat frontal cortex
Poster sessions (decline on 35.9%, p = 0.08). After INH-2 the same changes were registered only in males and just with tendency to significance (decline on 35.9%, p = 0.07). Also males survived antenatal INH-2 and females survived INH-1 demonstrated the significant elevation in time of grooming (increase on 57.4% and 65.4, respectively). According to data observed rats’ offspring of both sexes subjected to antenatal intermittent normobaric hypoxia was characterized by the increased anxiety and the decreased motor and exploratory activity independently of stress duration. Nevertheless single episode of antenatal intermittent normobaric hypoxia resulted in more wellmarked consequences for rats’ behavior, than doubled one. It could be connected with some kind of maternal adaptation for repeated stress influence. Furthermore as male offspring of both experimental groups showed more number of shifted indices, we can conclude that males were more sensible to antenatal stress, than females. Reference(s) [1] Trofimova, L.K., Maslova, M.V., Graf, A.V., et al, 2008 Effects of Antenatal Hypoxic Stress of Different Etiologies on Males: Correlation between Behavioral Patterns and Changes in Antioxidant Protection Activity and GABA Metabolism. Neurochemical Journal 2, 1−2, 72−75. [2] Trofimova, L.K., Graf, A.V., Maslova, M.V., et al, 2008 Influence of Antenatal Intermittent Normobaric Hypoxia during Early Organogenesis on the Development of White Rats. Biology Bulletin 3, 365–368.
P.4.04 Interaction between CRF and noradrenergic system in the rat frontal cortex B. Zieba1 ° , H. Domin1 , K. Stachowicz1 , M. Smialowska1 . Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, Krakow, Poland
1
Corticotropin-releasing factor (CRF) is a 41 amino acid neuropeptide which participates in the behavioral, neuroendocrine, and autonomic components of the stress response. In the brain CRF is localized in several structures: hypothalamus, amygdala and cerebral cortex. CRF exerts its action via two types of receptors CRF-R1 and CRF-R2. The CRF-R1 receptors are widely distributed in the brain, but in large amounts is in the frontal cortex. Noradrenaline (NA) is a catecholamine with dual roles as a neurotransmitter and a hormone. NA is synthesized from dopamine by dopamine-bhydroxylase in the central nervous system and peripheral sympathetic nervous system where NA is released from
S159
noradrenergic neurons. The actions of NA are carried out by activation of adrenergic receptors. Centrally administered CRF stimulates the release of noradrenaline in the brain (Lavicky and Dunn, 1993). These observations suggest a functional interaction between CRF system and noradrenergic neurons in the brain. Our earlier experiments indicated that CRF in dose of 0.2 ug/ul injected into the frontal cortex produced a significant anxiolytic effect in the elevated plus maze (EPM) test and this effect is mediated by CRF-R1 receptor (Zieba et al., 2008). The aim of present study was to investigate whether the noradrenergic system participates in the anxiolytic like effect of CRF in the frontal cortex. The experiments were performed on male Wistar rats weighing about 220–250 g, kept under standard laboratory conditions. The animals were stereotaxically implanted with cannulae directed bilaterally to the frontal cortex. Stereotaxic coordinates for the administration site were: AP = +3.2 mm, L = +2.0 mm, H = −1.4 mm from the Bregma, according to the Paxinos & Watson stereotaxic atlas. A few days (5−7) after surgery, CRF in a dose of 0.2 ug/ul was injected into the frontal cortex. Prazosin hydrochloride (alpha1 receptor antagonist) was administered intacortically (i.c.) in a dose of 0.1 ug/ul or intraperitoneally (i.p.) in a dose of 3 mg/kg. Prazosin was given intacortically about 30 sec before CRF injection, or it was given intraperitoneally 30 min before CRF injection. Then the rats’ behaviour was tested in the elevated plusmaze (EPM) 30 min after microinjection of CRF. Control rats received distilled water. It was found that CRF in a dose of 0.2 ug/ul produced anxiolytic like effect. This effect was significantly blocked by pretreatment with prazosin given i.p or i.c. Prazosin given alone did not induce any significant response on anxiety. The previous and present results suggest that in the frontal cortex CRF plays modulatory, anti-anxiety role, which is mediated by CRF-R1 receptor and the noradrenergic system is also engaged, via alpha1 receptors, in these anxiolytic like effects of CRF. Acknowledgements: The study was supported by Statutory Funds of the Institute of Pharmacology PAS, Cracow, Poland. All experimental procedures were approved by Animal Care and Use Committee at the Institute of Pharmacology PAS. Reference(s) [1] Lavicky, J., Dunn, A.J., 1993 Corticotropin-releasing factor stimulates catecholamine release in hypothalamus and prefrontal cortex in freely moving rats as assessed by microdialysis. J Neurochem. 60(2): 602−12.
S160
Poster sessions
[2] Zieba, B., Grzegorzewska, M., Branski, P., Domin, H., Wieronska, J.M., Hess, G., Smialowska, M., 2008 The behavioural and electrophysiological effects of CRF in rat frontal cortex. Neuropeptides 42(5−6): 513−23.
P.4.05 Trends in use of diazepam in university hospital V. Adomaitiene1 ° , B. Varanaviciene2 , O. Anciulyte3 . Medical University of Kaunas, Psychiatry, Kaunas, Lithuania; 2 Medical University of Kaunas, Central clinical pharmacy, Kaunas, Lithuania; 3 Medical University of Kaunas, Psychiatry, Kaunas, Lithuania
1
Introduction: Excessive benzodiazepine use is a public health concern from clinical and economical perspectives. Diazepam is one of widely used benzodiazepines in clinical practice. The main indications for its use are: anxiety disorders, sedation, premedication before interventional and surgical procedures; insomnia (for short term use); acute alcoholic abstinention, epileptical condition, febrile cramps, spasms of skeletal muscles. The defined daily dose (DDD) is an artificially and arbitrarily created statistical measurement used for research purposes in comparing the utilization of drugs. The formal definition of the DDD is “the assumed average maintenance dose per day for a drugs used for its main indication in adults”. DDD’s are assigned only to drugs that have already been provided with an ATC code. Ultimately, the DDD results in the numerical identification of the amount of drug product consumed per day, per 1000 residents. It is useful in determining the change in drug use over the time of a particular nation. It is also very useful for comparing consumption to identify overuse, underuse and misuse. Purpose of the study: The main goal of this study was to evaluate use of Diazepam as most widely used benzodiazepine in university hospital during 2007 and 2008 years and compare those data between themselves. Material and Methods: This pharmacoepidemiological analysis was performed in Lithuanian university hospital. The DDD analysis was performed to express consumption per every 1000 OBD for different clinical departmens. Average mean of DDD/1000 OBD was estimated for 2006–2007 years and values compared among those two years. Purpose was to evaluate trends in use of Diazepam in different department sections and review its use according indications in patient’s clinical cases. DDD of Diazepam is 10 mg. During this research data from central university hospital was used. Results: Data DDD/1000 OBD during two years (2007 and 2007) was compared. There were 2467.6
DDD/1000 OBD in neurosurgery department, 1822.5 in plastic surgery department, 888.1 in angiosurgery department, 751.7 in children reanimation department, 658.9 in mixed traumatology section during 2006 year. In comparison during 2007 year there were: 3226.0 in neurosurgery reanimation, 1574.8 in plastical surgery department, 748.4 in angiosurgery department, 714.0 in psychiatry department, 695.4 in head trauma’s department. From this data we see that use of Diazepam is remaining huge, and there is a tendency of its increasing. We should attempt the fact that huge rates of serious patients with difficult conditions and rare or complicated diseases are treated in university hospital as in the third level hospital. Conclusions: This analysis leads to a need of more detail medical cases researches with aim to evaluate indications and rational use of Diazepam in different sections of university hospital. Needs for future research for pharmacoeconomical evaluation for more effective use of Diazepam not only from medical, but from financial side. Reference(s) [1] Eandi, Mario. Drug Consumption Units and Pharmacoeconomic Evaluations: Use and Misuse of DDD and PDD. Drug Economics and Therapeutics Courses 2003; 3(4): 209–222. [2] WHO Center for Drug Statistics Methodology. Guidelines on ATC/DDD use. 2004. P.4.06 Trazodone − efficacious way to treat adjustment disorders P. Galecki1 ° , K. Bobinska1 , K. Zboralski1 , D. Berent1 , A. Florkowski1 . 1 Medical University, Department of Adult Psychiatry, Lodz, Poland Introduction: There are a great number of traumatic and stressful events that people are exposed to in the contemporary world. The response to them is the subjectively felt stress and numerous emotional reactions with anxiety and lowering of the mood. These symptoms substantially limit the ability of social and vocational performance. Their appearance allow to diagnose adjustment disorders. Adjustment disorders is an extremely common problem in general practice. The great majority of suffered patients are treated by the general practitioner. Serious physical disease or threat of suffering from it, death of close related individual, miscarriage, lost of social reliance because of migration are the most frequent reasons of adjustment disorders. According to many authors higher risk of civilization threats and breakdown
P.4.04 Interaction between CRF and noradrenergic system in the rat frontal cortex B. Zieba1 ° , H. Domin1 , K. Stachowicz1 , M. Smialowska1 . Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, Krakow, Poland
1
Corticotropin-releasing factor (CRF) is a 41 amino acid neuropeptide which participates in the behavioral, neuroendocrine, and autonomic components of the stress response. In the brain CRF is localized in several structures: hypothalamus, amygdala and cerebral cortex. CRF exerts its action via two types of receptors CRF-R1 and CRF-R2. The CRF-R1 receptors are widely distributed in the brain, but in large amounts is in the frontal cortex. Noradrenaline (NA) is a catecholamine with dual roles as a neurotransmitter and a hormone. NA is synthesized from dopamine by dopamine-bhydroxylase in the central nervous system and peripheral sympathetic nervous system where NA is released from
S159
noradrenergic neurons. The actions of NA are carried out by activation of adrenergic receptors. Centrally administered CRF stimulates the release of noradrenaline in the brain (Lavicky and Dunn, 1993). These observations suggest a functional interaction between CRF system and noradrenergic neurons in the brain. Our earlier experiments indicated that CRF in dose of 0.2 ug/ul injected into the frontal cortex produced a significant anxiolytic effect in the elevated plus maze (EPM) test and this effect is mediated by CRF-R1 receptor (Zieba et al., 2008). The aim of present study was to investigate whether the noradrenergic system participates in the anxiolytic like effect of CRF in the frontal cortex. The experiments were performed on male Wistar rats weighing about 220–250 g, kept under standard laboratory conditions. The animals were stereotaxically implanted with cannulae directed bilaterally to the frontal cortex. Stereotaxic coordinates for the administration site were: AP = +3.2 mm, L = +2.0 mm, H = −1.4 mm from the Bregma, according to the Paxinos & Watson stereotaxic atlas. A few days (5−7) after surgery, CRF in a dose of 0.2 ug/ul was injected into the frontal cortex. Prazosin hydrochloride (alpha1 receptor antagonist) was administered intacortically (i.c.) in a dose of 0.1 ug/ul or intraperitoneally (i.p.) in a dose of 3 mg/kg. Prazosin was given intacortically about 30 sec before CRF injection, or it was given intraperitoneally 30 min before CRF injection. Then the rats’ behaviour was tested in the elevated plusmaze (EPM) 30 min after microinjection of CRF. Control rats received distilled water. It was found that CRF in a dose of 0.2 ug/ul produced anxiolytic like effect. This effect was significantly blocked by pretreatment with prazosin given i.p or i.c. Prazosin given alone did not induce any significant response on anxiety. The previous and present results suggest that in the frontal cortex CRF plays modulatory, anti-anxiety role, which is mediated by CRF-R1 receptor and the noradrenergic system is also engaged, via alpha1 receptors, in these anxiolytic like effects of CRF. Acknowledgements: The study was supported by Statutory Funds of the Institute of Pharmacology PAS, Cracow, Poland. All experimental procedures were approved by Animal Care and Use Committee at the Institute of Pharmacology PAS. Reference(s) [1] Lavicky, J., Dunn, A.J., 1993 Corticotropin-releasing factor stimulates catecholamine release in hypothalamus and prefrontal cortex in freely moving rats as assessed by microdialysis. J Neurochem. 60(2): 602−12.
S160
Poster sessions
[2] Zieba, B., Grzegorzewska, M., Branski, P., Domin, H., Wieronska, J.M., Hess, G., Smialowska, M., 2008 The behavioural and electrophysiological effects of CRF in rat frontal cortex. Neuropeptides 42(5−6): 513−23.
P.4.05 Trends in use of diazepam in university hospital V. Adomaitiene1 ° , B. Varanaviciene2 , O. Anciulyte3 . Medical University of Kaunas, Psychiatry, Kaunas, Lithuania; 2 Medical University of Kaunas, Central clinical pharmacy, Kaunas, Lithuania; 3 Medical University of Kaunas, Psychiatry, Kaunas, Lithuania
1
Introduction: Excessive benzodiazepine use is a public health concern from clinical and economical perspectives. Diazepam is one of widely used benzodiazepines in clinical practice. The main indications for its use are: anxiety disorders, sedation, premedication before interventional and surgical procedures; insomnia (for short term use); acute alcoholic abstinention, epileptical condition, febrile cramps, spasms of skeletal muscles. The defined daily dose (DDD) is an artificially and arbitrarily created statistical measurement used for research purposes in comparing the utilization of drugs. The formal definition of the DDD is “the assumed average maintenance dose per day for a drugs used for its main indication in adults”. DDD’s are assigned only to drugs that have already been provided with an ATC code. Ultimately, the DDD results in the numerical identification of the amount of drug product consumed per day, per 1000 residents. It is useful in determining the change in drug use over the time of a particular nation. It is also very useful for comparing consumption to identify overuse, underuse and misuse. Purpose of the study: The main goal of this study was to evaluate use of Diazepam as most widely used benzodiazepine in university hospital during 2007 and 2008 years and compare those data between themselves. Material and Methods: This pharmacoepidemiological analysis was performed in Lithuanian university hospital. The DDD analysis was performed to express consumption per every 1000 OBD for different clinical departmens. Average mean of DDD/1000 OBD was estimated for 2006–2007 years and values compared among those two years. Purpose was to evaluate trends in use of Diazepam in different department sections and review its use according indications in patient’s clinical cases. DDD of Diazepam is 10 mg. During this research data from central university hospital was used. Results: Data DDD/1000 OBD during two years (2007 and 2007) was compared. There were 2467.6
DDD/1000 OBD in neurosurgery department, 1822.5 in plastic surgery department, 888.1 in angiosurgery department, 751.7 in children reanimation department, 658.9 in mixed traumatology section during 2006 year. In comparison during 2007 year there were: 3226.0 in neurosurgery reanimation, 1574.8 in plastical surgery department, 748.4 in angiosurgery department, 714.0 in psychiatry department, 695.4 in head trauma’s department. From this data we see that use of Diazepam is remaining huge, and there is a tendency of its increasing. We should attempt the fact that huge rates of serious patients with difficult conditions and rare or complicated diseases are treated in university hospital as in the third level hospital. Conclusions: This analysis leads to a need of more detail medical cases researches with aim to evaluate indications and rational use of Diazepam in different sections of university hospital. Needs for future research for pharmacoeconomical evaluation for more effective use of Diazepam not only from medical, but from financial side. Reference(s) [1] Eandi, Mario. Drug Consumption Units and Pharmacoeconomic Evaluations: Use and Misuse of DDD and PDD. Drug Economics and Therapeutics Courses 2003; 3(4): 209–222. [2] WHO Center for Drug Statistics Methodology. Guidelines on ATC/DDD use. 2004. P.4.06 Trazodone − efficacious way to treat adjustment disorders P. Galecki1 ° , K. Bobinska1 , K. Zboralski1 , D. Berent1 , A. Florkowski1 . 1 Medical University, Department of Adult Psychiatry, Lodz, Poland Introduction: There are a great number of traumatic and stressful events that people are exposed to in the contemporary world. The response to them is the subjectively felt stress and numerous emotional reactions with anxiety and lowering of the mood. These symptoms substantially limit the ability of social and vocational performance. Their appearance allow to diagnose adjustment disorders. Adjustment disorders is an extremely common problem in general practice. The great majority of suffered patients are treated by the general practitioner. Serious physical disease or threat of suffering from it, death of close related individual, miscarriage, lost of social reliance because of migration are the most frequent reasons of adjustment disorders. According to many authors higher risk of civilization threats and breakdown