- Email: [email protected]
Plasma-delta-sleep-inducing peptide (DSIP) and plasma-neuropeptide Y (NPY) in suicide attempters
48S
Poster session I
BIOL. PSYCHIATRY 1997;42:15-2975
\14-1461 Neurotropic effects of some exorphlns-natural
114-1491 Is sulcldality correlated with hypothalamic-pituitary-adrenocortical (HPA)-system related peptides?
exogenous oplold peptides N.Yu. Sokhanenkova, L.S. Asmakova, VA Dubinln, J.D. Bespalova, A.A. Kamensky. Department of Human and Animal Physiology, Faculty of Biology, Moscow State University, Moscow, Russia Despite the presence of N-tennlnal tyrosine and the ability to bind JL" and a-receptors (Koch, Brantl, 1990), exorphlns exhibit not only characteristic but noncharacteristlc for typical opiold peptldes properties. Methods: The Influence of wheat gluten, hemoglobin and milk tl-easein fragments: exorphin C (YPISL), hemorphin (YPWTER) and p-easomorphln (yPFPGPI), (intraperitoneal, 5 and 20 mglkg) on pain sensitivity, locomotion and anxiety 01 white rats was analysed Results: Exorphln C and hemorphln (both doses) exhibited hyperalgesic effect and Increased rats anxiety. On the contrary p-easomorphin decreased anxiety and pain sensitivity. All peptides In dose 20 mglkg slightly decreased locomotion and orientative activity of rats. More typical opiold properties of p-easomorphln are probably detennined by It's exohonnone function on early stages of mammal ontogeny (Umbach et aI., 1985). Exorphln C and hemorphin can be characterized as functional antagonists of endogenous oploids. It Is possible that some unexpected neurotropic effects of food proteins are connected with the Influence of investigated peptides.
114-1471 Study of neurotropic activity of ACTH[S-7]
A. Westrin "
A. Ekman 2, G. Regnell'. Lil. Tril.skman-Bendz 1. ' Dept of Psychiatry. University Hospital, Lund, Sweden, 2 Dept of Psychiatry and Neurochemistry. University of Gothenburg, Gothenburg, Sweden
Methods: Corticotropin-releasing honnone (CRH), delta-sleep-Inducing peptide (DSIP) and somatostatin (SOM) In the cerebrospinal fluid (CSF) and the Suicidal Assessment Scale (SAS) were measured repeatedly in 21 suicide attempters (6 males, 15 females). They were diagnosed as major depressive disorder (MOD, N 7), dystymia (N 7), and other diagnoses (N = 7). The first investigation (index) was perfonned at wash out, a couple of weeks after a suicide attempt. The patients were followed every third month during one to two years. Results: At index, DSIP was significantly and negatively correlated with SAS-scores. When using repeated measures, SOM was significantly higher at maximum of SAS-scores than at minimum. In patients with other diagnoses than MOD, negative correlations between SOM levels and SAS-scores were more common than positive correlations. No significant correlations between CRH and SAS-scores appeared. Conclusions: When comparing patients at baseline, CSF- OSIP may mirror suicidality. Over time, CSF-SOM of nonMDD patients seems to change along with scores of suicidality. CSFoCRH does not seem to be related to rated suicidality.
=
=
structural analog-tripeptide ERP N.G. Levitskaya. M.G. Uranova, O.G. Voskresenskaya, N.S. Pridatko, V.N. Nezavibatko, A.A. Kamensky. Department of Human and Animal Physiology, Faculty of Biology, Moscow State University, Moscow, Russia The neurotropic activity of the tripeptide Glu-Arg-Pro (ERP), a structural analog of ACTH(5-7}, was Investigated In white rats. Methods: The effects on leaming of ERP were Investigated In active and passive avoidance tasks. Orientative trying and emotional rate of animals were estimated in ·open field" and "ole board" tests. Results: Intraperitoneal injection of 0.15 mg/kg ERP 15 minutes prior to training Impaired acquisition of passive and active avoidance tasks. Post-training peptide Injection was Ineffective. It was also found that the peptide was able to decrease the rats response to stressoric stimUli. In addition it was shown that ERP blocked the Influence of reserpine and mildly Increased that of amlnasin. Based on the results obtained, the neurotropic effects of ERP were due to the Influence on the perception of test conditions and on the estimation of biological significence of environmental stimuli. It seems likely that ERP effects Involve the biogenic amines system.
114-1481 Effects of PACAP on sleep EEG and nocturnal hormone secretion In men I.A. Antonljevic, H. Murck, A.M. FrieOOes, S. Bohlhaller, T. Schier, A. Steiger. Max Planck Institute of Psychiatry. Dept. of Psychiatry, Munich, Germany Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely dis• tributed In the CNS with highest levels in the hypothalamus. Since 1) PACAP shares 68% homology with the vasolntestinal peptide (VIP) family and 2} VIP Increases both REM and nonREM sleep (Murck H. et aI. Am J PhysioI1996), we Investigated the effects of 4 bolus Injections of PACAP (12.5 /Lg each, at hourly between 220CHl1oo h) or saline on noctumal sleep and honnone secretion In 7 young men. The sleep EEG was recorded (2300-0700 h) and plasma samples were assayed for growth hormone (GH), prolactin (PRL) and cortisol. Following PACAP, the secretion of GH and cortisol was not affected, while PRL levels showed a trend to decrease during the 1st half of the night. Sleep-EEG analysis showed a significant decrease In slow wave sleep (SWS) during the 111 , but an Increase In the 4th sleep cycle. Since REM sleep was firstly Increased and then decreased during the night. the ratio of REMINREM sleep was significantly decreased for the 4t1l sleep cycle (0.61 ± 0.08 vs. 0.34 ± O.OS). In summary, PACAP affected the distribution of SWS and REM sleep during the nIght in men. Since these effects were different from those obtained with VIP, our data suggest that the effects of VIP and PACAP on human sleep are not mediated by the same receptor.
114-150 I Effects of pentylenetetrazole-Induced kindling on the thyrotropin-releasing hormone biosynthesis and receptors In the rat brain L. Jaworska-Feil, J. Turchan', B. Przewlocka " B. Budziszewska, M. Lesklewicz, W. Lason. Department of Endocrinology, , Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Smetna 12, CICICOW, Poland Thyrotropin releasing honnone (TRH) is Involved In modulation of ex• perimental epileptogenesis. Biochemical data Indicate that electrically and chemically evoked seizures enhance the TRH biosynthesis In the hippocam• pus; however. less Is known about seizure-related changes In TRH In Other brain structures. In order to resolve this problem, in a lime-course study we investigated effects of the pentylenetetrazole (PTZ) -induced kindling (40 mg/kg I.p. daily for 7 days) on the TRH level, prepro-TRH (ppTRH) mRNA and TRH receptors in the rat brain. As shown by an In situ hybridization, the ppTRH mRNA level was elevated in the pyrifonn cortex at 3 and 24 hr after the last PTZ injection, whereas the level of TRH In that structure remained unchanged. PTZ·kindled rats showed an enhanced TRH level in the striatum after 24 hr only, that effect being associated with a decrease in the Bmox of TRH receptors. No changes In the TRH level or receptors were found In amygdala of kindled rats. After 7 days only an Increase in the TRH receptor Bma>< and Kct In the pyrifonn cortex was observed, whereas on day 15 no significant changes were seen In any biochemical parameters. The above data indicate that the TRH system may participate in the regulation of kindled seizures, but is not involved In the mechanism of pennanent seizure susceptibility, characteristic of this model.
I
114-151 Plasma-delta-sleep-Induclng peptide (DSIP) and plasma-neuropeptide Y (NPY) In suicide attempters
A. Westrin "
A. Ekman 2, L Tril.askman-Bendz 1. 1 Dept. of Psychiatry. University Hospital, Lund, Sweden, 2 Dept. of Psychiatry. University of Gothenburg, Gothenburg, Sweden, Dept. of Neurochemistry. University of Gothenburg, Gothenburg. Sweden
The aim of this study was to explore p-DSIP and p-NPY In the dexametha_ sone suppression test (DST) In suicide altempters. Methods: P-DSIP, p-NPY and serum (s}-cortisol were measured In the OST In 34 suicidal patients and In 34 healthy age- and sexmatched controls. Results: At baseline the patients had significantly higher p-DSIP and s-CQrtisol and significantly lower p-NPY than the controls. Patients with previous suicide attempts had significantly higher p-DSIP and significantly lower p-NPY than "firsttimers". Patients with major depressive diSOrder (MOD) had significantly higher p-DSIP than the other patients. At baseline p-NPY correlated significantly with cortisol in patients with depression NOS' There was atrend towards a dual effect 01 dexamethasone on p-DSIP levels:
Poster session I
Conclusion: These observations Indicate a role lor DSIP In the hypotha. Iamic-pitultary-adrenocortical·axis and In MDD patients. Both DSIP and NPY seem to be of interest when studying repeated suicide behaviour.
\14-1521 Plasma neuropeptlde Y reactivity to cholecystokinin challenge In panic disorders and normal controls J.P. Boulenger, I. Jerabek. J. Bradwijn. Y.J. Lavallee, A. cadieux. Departement de psychiatrie de I'Universite de Sherbrooke, Centre Universitaire de Sante de L:Estrie, 555, rue Murray. Sherbrooke, Quebec, canade JIG 2K8 Neuropeptide Y (NPY) Is a pancreatic polypeptide widely distributed through• out the peripheral and the central nervous system with very high amounts In areas related to the regulation of emotions (amygdala). arousal (lOCUS coeruleus) and sympathetic activity (hypothalamus). In many places NPY coexists with either norepinephrine or epinephrine and modulates the re• lease and/or the effects of catecholamlnes. especially In cases 01 Intense or chronic stimulation. The results 01 a preliminary study suggested that baseline plasma NPY·like Immunoreactivity (NPY-II) was Increased In panic disorder (PO) patients compared to normal controls and positively corre• lated with the duration of their disorder. In this experiment we measured plasma NPY-II at various times before and alter IV administration 01 25 I'g 01 cholecystokinin tetrapeptide (CCK-4) another Intestinal neuropeptide knoWn to Induce panic attacks In both normal controls and PO patients. The effects 01 CCK-4 were compared to those of a placebo in a double-blind, cross-over experiment where the order 01 administration of these substances was randomized. Two groups participated to this study: (1) a group 0116 normal controls (11 males; 5 females; mean age: 29); (2) a group 01 12 patients fulfilling DSM IV criteria lor panic disorder (11 females; 1 male; mean age: 26) but without depressive comorbldity. In contrast to placebo CCK-4 (induced a significant Increase in plasma NPY·Ii. 5 to 10 min alter IV administration, while most of the anxiety symptoms took place dUring the first 5 min. There was not significant differences In NPY-Ji reactivity to the challenge between the 2 groups. Results conceming the relationships between NPY-Illncrease and the panlcogenic effects of CCK-4 will also be presented.
114-1531 Brain concentrations of amlnes and neuropeptlde Y-LJ following peripheral administration of Cholecystoklnln-4 A.-I<. Gilbert, I. Jerabek. M. 8olongo. J.P. Boulenger, A. cadieux, F.B. Jolicoeur. Departements de Psychiatrie and de Pharmacologie, Universit6 de Sherbrooke, Sherbrooke, Dc, Canada Peripheral administration of cholecystoklnlll4 (CC!<4) Induces panic-like symptoms In humans. To better understand this phenomenon, we have examined neurochemical effects of peripheraJly administered CC!<4 in rats. Methods: Fifteen min alter an intraperitoneal injection of CC!<4 (5 I'g), dissection of the following regions was performed: nucleus accumbens, striatum, septum, hypothalamus. hippocampus. amygdala, frontal cortex and prefrontal cortex. In each region, concentrations of dopamine (DA), serotonin (5-HT) and of the metabolites HVA. OOPAC and 5-HIAA. were measured by HPLC-ECD. In the same regions. concentrations of neuropeptide Y-Uke Immunoreactivity (NPY-U) were detemnined by radioimmunoassay. Results: Revealed prominent decreases In utilization of both DA and 5-HT In the prelrontal cortex, as estimated by metabolite-transmitter ratios. as well as a marked decrease In NPY·U concentrations in the nucleus accumbens. Conclusion: The results 01 the present study demonstrate that peripheral administration CC!<4 has important central actions as evidenced by selective and region-specific neurochemical changes. We are presently completing studies examining the effects of two other experimental stressors, physical restraint and cat odOr, on the same neurochemical parameters (Supported byFRSQ).
BIOL. PSYCHIATRY 1997;42: 15-297S
49S
114-1541 Human plasma NPY-Iike Immunoreactivity In patients with depressive and panic disorder A. Hermes 1• J.P. Boulenger 2. A. Cadieux 2. I. Jerabek 2. H. Cacl l • Y.J. Lavallee 2. G. Darcourt 1. 1 C/inique de Psychiatrie et de Psycho/egie Medica/e, H6pita/ Pasteur, Nice, France, 2 Centre Hospita/o Universitaire de Sherbrooke, Quebec, Canada The neuropeptide Y (NPY) is a 36 amino acid peptide. It's Involvement In the physiopathology of some psychiatric Illness has been olten advanoed. Biochemical studies report a strong functional assoclation with the nora• drenerglc system for both the central nerve system and the peripheral. The role of noradrenaline in anxlo-depressive disorder physiology has been well establish~
Methods: We carried out two studies In witch we evaluated NPY-Iike Immunoreactivity plasma peripheral levels on patients suffering !rom panic and depressive disorders (DSM III R criteria). In the first study we recruited 17 patients with a panic diso~er diagnosis and 41 controls. For the second second study, the population 'included 14 panic disorder, 19 depressive disorder and 10 healthy volunters. The dosage was realised with a radio• immuno-assay using an antiserum to human NPY. and 125 lode labeled NPY as a tracer. Results: We found markedly higher NPY-like Immunoreactivity in patients with panic disorder (p < 0.001). Then there was a statistically signifiant cor· relation between baseline plasma NPY-Iike Immunorectlvity and the duration of illness (r z 0.711 ; u < 0.005). For the second study we find reverse results. Although these findings are different, It's seems that the NPY Is Involved in the physiopathology of paniC disorder.
114-1551 Relationship between SCL-90, Maudsley Personality Inventory and CCK41nduced Intracellular calcium response In T cells J. Akiyoshi, C. Yamauchi. M. Furuta, S. Katsuragi. Y. Kohno. Y. Yamamoto, T. Tsutsuml. K. Isogawa. I. FujII. Dept. Neuropsychiatry, Oita Medical University. Hasama-Machi, Oits, Japan This study examined the relationship between SCL-90. Maudsley Personality Inventory and CCK-4-induced Intracellular celcium rasponse In T cells. Method: Fifty two normaJ volunteers were registered. Measures Included CCK-4-induced Intracellular calcium response in T cells, SCL-90 scores. and MPI. Results: Paranoid Ideation, or Interpersonal sensitivity In SeL·90 shoWed a significant negative association with CCK-4-lnduced Intracellular celcium response. MPI was not associated with CCK-4-induced Intracellular calclum response. CCKs receptor !unction might playa role in paranoid Ideation or Interpersonal sensitivity.
114-1561 The effects of delta sleep Inducing peptide on rats In accordance with their stress-sensitivity T.V. Strekalova. P.K. Anokh/n Institute of Normal Physiology. Moscow, Russia Our aim was to study the effects of Delta Sleep Inducing Peptide-DSIP- on burying behavior 01 rats with diverse stress-sensitivity. Methods: Firstly the correlation between aversive behavior features and somatic stress sensitivity In Wistar rats were studied. The aversive behavior was examine in electric-probe burying response model. when alter slight electric event (0.8-1.4 mAl In grid-floor cage the duration of exploration and freezing behavior, and the individual type of aversive strategy (active type - locomotor behavior. passive type - freezing reaction) were recorded for each rat. Then rats were submitted to 5-days stress session. The obtained data were evaluated by correlation analysis. The second aim was to check the effects of I.p. Injected DSIP (60 nMlkg) on behavioral characteristics raflected stress-sensitivity in Wlstar rats within the same behavior model. Results: The sUbjects with PBSSlve aversive stretegy and long freeZing duretion had a highest stress-sensitivity, and DSIP Improved their burying behavior. Contrary. In others the deficit of burying under the DSIP Influence was lound. Therefore. we conclude that effects of DSIP on aversive behavior In rats and their stress-sensitivity are linked.
Poster session I
BIOL. PSYCHIATRY 1997;42:15-2975
\14-1461 Neurotropic effects of some exorphlns-natural
114-1491 Is sulcldality correlated with hypothalamic-pituitary-adrenocortical (HPA)-system related peptides?
exogenous oplold peptides N.Yu. Sokhanenkova, L.S. Asmakova, VA Dubinln, J.D. Bespalova, A.A. Kamensky. Department of Human and Animal Physiology, Faculty of Biology, Moscow State University, Moscow, Russia Despite the presence of N-tennlnal tyrosine and the ability to bind JL" and a-receptors (Koch, Brantl, 1990), exorphlns exhibit not only characteristic but noncharacteristlc for typical opiold peptldes properties. Methods: The Influence of wheat gluten, hemoglobin and milk tl-easein fragments: exorphin C (YPISL), hemorphin (YPWTER) and p-easomorphln (yPFPGPI), (intraperitoneal, 5 and 20 mglkg) on pain sensitivity, locomotion and anxiety 01 white rats was analysed Results: Exorphln C and hemorphln (both doses) exhibited hyperalgesic effect and Increased rats anxiety. On the contrary p-easomorphin decreased anxiety and pain sensitivity. All peptides In dose 20 mglkg slightly decreased locomotion and orientative activity of rats. More typical opiold properties of p-easomorphln are probably detennined by It's exohonnone function on early stages of mammal ontogeny (Umbach et aI., 1985). Exorphln C and hemorphin can be characterized as functional antagonists of endogenous oploids. It Is possible that some unexpected neurotropic effects of food proteins are connected with the Influence of investigated peptides.
114-1471 Study of neurotropic activity of ACTH[S-7]
A. Westrin "
A. Ekman 2, G. Regnell'. Lil. Tril.skman-Bendz 1. ' Dept of Psychiatry. University Hospital, Lund, Sweden, 2 Dept of Psychiatry and Neurochemistry. University of Gothenburg, Gothenburg, Sweden
Methods: Corticotropin-releasing honnone (CRH), delta-sleep-Inducing peptide (DSIP) and somatostatin (SOM) In the cerebrospinal fluid (CSF) and the Suicidal Assessment Scale (SAS) were measured repeatedly in 21 suicide attempters (6 males, 15 females). They were diagnosed as major depressive disorder (MOD, N 7), dystymia (N 7), and other diagnoses (N = 7). The first investigation (index) was perfonned at wash out, a couple of weeks after a suicide attempt. The patients were followed every third month during one to two years. Results: At index, DSIP was significantly and negatively correlated with SAS-scores. When using repeated measures, SOM was significantly higher at maximum of SAS-scores than at minimum. In patients with other diagnoses than MOD, negative correlations between SOM levels and SAS-scores were more common than positive correlations. No significant correlations between CRH and SAS-scores appeared. Conclusions: When comparing patients at baseline, CSF- OSIP may mirror suicidality. Over time, CSF-SOM of nonMDD patients seems to change along with scores of suicidality. CSFoCRH does not seem to be related to rated suicidality.
=
=
structural analog-tripeptide ERP N.G. Levitskaya. M.G. Uranova, O.G. Voskresenskaya, N.S. Pridatko, V.N. Nezavibatko, A.A. Kamensky. Department of Human and Animal Physiology, Faculty of Biology, Moscow State University, Moscow, Russia The neurotropic activity of the tripeptide Glu-Arg-Pro (ERP), a structural analog of ACTH(5-7}, was Investigated In white rats. Methods: The effects on leaming of ERP were Investigated In active and passive avoidance tasks. Orientative trying and emotional rate of animals were estimated in ·open field" and "ole board" tests. Results: Intraperitoneal injection of 0.15 mg/kg ERP 15 minutes prior to training Impaired acquisition of passive and active avoidance tasks. Post-training peptide Injection was Ineffective. It was also found that the peptide was able to decrease the rats response to stressoric stimUli. In addition it was shown that ERP blocked the Influence of reserpine and mildly Increased that of amlnasin. Based on the results obtained, the neurotropic effects of ERP were due to the Influence on the perception of test conditions and on the estimation of biological significence of environmental stimuli. It seems likely that ERP effects Involve the biogenic amines system.
114-1481 Effects of PACAP on sleep EEG and nocturnal hormone secretion In men I.A. Antonljevic, H. Murck, A.M. FrieOOes, S. Bohlhaller, T. Schier, A. Steiger. Max Planck Institute of Psychiatry. Dept. of Psychiatry, Munich, Germany Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely dis• tributed In the CNS with highest levels in the hypothalamus. Since 1) PACAP shares 68% homology with the vasolntestinal peptide (VIP) family and 2} VIP Increases both REM and nonREM sleep (Murck H. et aI. Am J PhysioI1996), we Investigated the effects of 4 bolus Injections of PACAP (12.5 /Lg each, at hourly between 220CHl1oo h) or saline on noctumal sleep and honnone secretion In 7 young men. The sleep EEG was recorded (2300-0700 h) and plasma samples were assayed for growth hormone (GH), prolactin (PRL) and cortisol. Following PACAP, the secretion of GH and cortisol was not affected, while PRL levels showed a trend to decrease during the 1st half of the night. Sleep-EEG analysis showed a significant decrease In slow wave sleep (SWS) during the 111 , but an Increase In the 4th sleep cycle. Since REM sleep was firstly Increased and then decreased during the night. the ratio of REMINREM sleep was significantly decreased for the 4t1l sleep cycle (0.61 ± 0.08 vs. 0.34 ± O.OS). In summary, PACAP affected the distribution of SWS and REM sleep during the nIght in men. Since these effects were different from those obtained with VIP, our data suggest that the effects of VIP and PACAP on human sleep are not mediated by the same receptor.
114-150 I Effects of pentylenetetrazole-Induced kindling on the thyrotropin-releasing hormone biosynthesis and receptors In the rat brain L. Jaworska-Feil, J. Turchan', B. Przewlocka " B. Budziszewska, M. Lesklewicz, W. Lason. Department of Endocrinology, , Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Smetna 12, CICICOW, Poland Thyrotropin releasing honnone (TRH) is Involved In modulation of ex• perimental epileptogenesis. Biochemical data Indicate that electrically and chemically evoked seizures enhance the TRH biosynthesis In the hippocam• pus; however. less Is known about seizure-related changes In TRH In Other brain structures. In order to resolve this problem, in a lime-course study we investigated effects of the pentylenetetrazole (PTZ) -induced kindling (40 mg/kg I.p. daily for 7 days) on the TRH level, prepro-TRH (ppTRH) mRNA and TRH receptors in the rat brain. As shown by an In situ hybridization, the ppTRH mRNA level was elevated in the pyrifonn cortex at 3 and 24 hr after the last PTZ injection, whereas the level of TRH In that structure remained unchanged. PTZ·kindled rats showed an enhanced TRH level in the striatum after 24 hr only, that effect being associated with a decrease in the Bmox of TRH receptors. No changes In the TRH level or receptors were found In amygdala of kindled rats. After 7 days only an Increase in the TRH receptor Bma>< and Kct In the pyrifonn cortex was observed, whereas on day 15 no significant changes were seen In any biochemical parameters. The above data indicate that the TRH system may participate in the regulation of kindled seizures, but is not involved In the mechanism of pennanent seizure susceptibility, characteristic of this model.
I
114-151 Plasma-delta-sleep-Induclng peptide (DSIP) and plasma-neuropeptide Y (NPY) In suicide attempters
A. Westrin "
A. Ekman 2, L Tril.askman-Bendz 1. 1 Dept. of Psychiatry. University Hospital, Lund, Sweden, 2 Dept. of Psychiatry. University of Gothenburg, Gothenburg, Sweden, Dept. of Neurochemistry. University of Gothenburg, Gothenburg. Sweden
The aim of this study was to explore p-DSIP and p-NPY In the dexametha_ sone suppression test (DST) In suicide altempters. Methods: P-DSIP, p-NPY and serum (s}-cortisol were measured In the OST In 34 suicidal patients and In 34 healthy age- and sexmatched controls. Results: At baseline the patients had significantly higher p-DSIP and s-CQrtisol and significantly lower p-NPY than the controls. Patients with previous suicide attempts had significantly higher p-DSIP and significantly lower p-NPY than "firsttimers". Patients with major depressive diSOrder (MOD) had significantly higher p-DSIP than the other patients. At baseline p-NPY correlated significantly with cortisol in patients with depression NOS' There was atrend towards a dual effect 01 dexamethasone on p-DSIP levels:
Poster session I
Conclusion: These observations Indicate a role lor DSIP In the hypotha. Iamic-pitultary-adrenocortical·axis and In MDD patients. Both DSIP and NPY seem to be of interest when studying repeated suicide behaviour.
\14-1521 Plasma neuropeptlde Y reactivity to cholecystokinin challenge In panic disorders and normal controls J.P. Boulenger, I. Jerabek. J. Bradwijn. Y.J. Lavallee, A. cadieux. Departement de psychiatrie de I'Universite de Sherbrooke, Centre Universitaire de Sante de L:Estrie, 555, rue Murray. Sherbrooke, Quebec, canade JIG 2K8 Neuropeptide Y (NPY) Is a pancreatic polypeptide widely distributed through• out the peripheral and the central nervous system with very high amounts In areas related to the regulation of emotions (amygdala). arousal (lOCUS coeruleus) and sympathetic activity (hypothalamus). In many places NPY coexists with either norepinephrine or epinephrine and modulates the re• lease and/or the effects of catecholamlnes. especially In cases 01 Intense or chronic stimulation. The results 01 a preliminary study suggested that baseline plasma NPY·like Immunoreactivity (NPY-II) was Increased In panic disorder (PO) patients compared to normal controls and positively corre• lated with the duration of their disorder. In this experiment we measured plasma NPY-II at various times before and alter IV administration 01 25 I'g 01 cholecystokinin tetrapeptide (CCK-4) another Intestinal neuropeptide knoWn to Induce panic attacks In both normal controls and PO patients. The effects 01 CCK-4 were compared to those of a placebo in a double-blind, cross-over experiment where the order 01 administration of these substances was randomized. Two groups participated to this study: (1) a group 0116 normal controls (11 males; 5 females; mean age: 29); (2) a group 01 12 patients fulfilling DSM IV criteria lor panic disorder (11 females; 1 male; mean age: 26) but without depressive comorbldity. In contrast to placebo CCK-4 (induced a significant Increase in plasma NPY·Ii. 5 to 10 min alter IV administration, while most of the anxiety symptoms took place dUring the first 5 min. There was not significant differences In NPY-Ji reactivity to the challenge between the 2 groups. Results conceming the relationships between NPY-Illncrease and the panlcogenic effects of CCK-4 will also be presented.
114-1531 Brain concentrations of amlnes and neuropeptlde Y-LJ following peripheral administration of Cholecystoklnln-4 A.-I<. Gilbert, I. Jerabek. M. 8olongo. J.P. Boulenger, A. cadieux, F.B. Jolicoeur. Departements de Psychiatrie and de Pharmacologie, Universit6 de Sherbrooke, Sherbrooke, Dc, Canada Peripheral administration of cholecystoklnlll4 (CC!<4) Induces panic-like symptoms In humans. To better understand this phenomenon, we have examined neurochemical effects of peripheraJly administered CC!<4 in rats. Methods: Fifteen min alter an intraperitoneal injection of CC!<4 (5 I'g), dissection of the following regions was performed: nucleus accumbens, striatum, septum, hypothalamus. hippocampus. amygdala, frontal cortex and prefrontal cortex. In each region, concentrations of dopamine (DA), serotonin (5-HT) and of the metabolites HVA. OOPAC and 5-HIAA. were measured by HPLC-ECD. In the same regions. concentrations of neuropeptide Y-Uke Immunoreactivity (NPY-U) were detemnined by radioimmunoassay. Results: Revealed prominent decreases In utilization of both DA and 5-HT In the prelrontal cortex, as estimated by metabolite-transmitter ratios. as well as a marked decrease In NPY·U concentrations in the nucleus accumbens. Conclusion: The results 01 the present study demonstrate that peripheral administration CC!<4 has important central actions as evidenced by selective and region-specific neurochemical changes. We are presently completing studies examining the effects of two other experimental stressors, physical restraint and cat odOr, on the same neurochemical parameters (Supported byFRSQ).
BIOL. PSYCHIATRY 1997;42: 15-297S
49S
114-1541 Human plasma NPY-Iike Immunoreactivity In patients with depressive and panic disorder A. Hermes 1• J.P. Boulenger 2. A. Cadieux 2. I. Jerabek 2. H. Cacl l • Y.J. Lavallee 2. G. Darcourt 1. 1 C/inique de Psychiatrie et de Psycho/egie Medica/e, H6pita/ Pasteur, Nice, France, 2 Centre Hospita/o Universitaire de Sherbrooke, Quebec, Canada The neuropeptide Y (NPY) is a 36 amino acid peptide. It's Involvement In the physiopathology of some psychiatric Illness has been olten advanoed. Biochemical studies report a strong functional assoclation with the nora• drenerglc system for both the central nerve system and the peripheral. The role of noradrenaline in anxlo-depressive disorder physiology has been well establish~
Methods: We carried out two studies In witch we evaluated NPY-Iike Immunoreactivity plasma peripheral levels on patients suffering !rom panic and depressive disorders (DSM III R criteria). In the first study we recruited 17 patients with a panic diso~er diagnosis and 41 controls. For the second second study, the population 'included 14 panic disorder, 19 depressive disorder and 10 healthy volunters. The dosage was realised with a radio• immuno-assay using an antiserum to human NPY. and 125 lode labeled NPY as a tracer. Results: We found markedly higher NPY-like Immunoreactivity in patients with panic disorder (p < 0.001). Then there was a statistically signifiant cor· relation between baseline plasma NPY-Iike Immunorectlvity and the duration of illness (r z 0.711 ; u < 0.005). For the second study we find reverse results. Although these findings are different, It's seems that the NPY Is Involved in the physiopathology of paniC disorder.
114-1551 Relationship between SCL-90, Maudsley Personality Inventory and CCK41nduced Intracellular calcium response In T cells J. Akiyoshi, C. Yamauchi. M. Furuta, S. Katsuragi. Y. Kohno. Y. Yamamoto, T. Tsutsuml. K. Isogawa. I. FujII. Dept. Neuropsychiatry, Oita Medical University. Hasama-Machi, Oits, Japan This study examined the relationship between SCL-90. Maudsley Personality Inventory and CCK-4-induced Intracellular celcium rasponse In T cells. Method: Fifty two normaJ volunteers were registered. Measures Included CCK-4-induced Intracellular calcium response in T cells, SCL-90 scores. and MPI. Results: Paranoid Ideation, or Interpersonal sensitivity In SeL·90 shoWed a significant negative association with CCK-4-lnduced Intracellular celcium response. MPI was not associated with CCK-4-induced Intracellular calclum response. CCKs receptor !unction might playa role in paranoid Ideation or Interpersonal sensitivity.
114-1561 The effects of delta sleep Inducing peptide on rats In accordance with their stress-sensitivity T.V. Strekalova. P.K. Anokh/n Institute of Normal Physiology. Moscow, Russia Our aim was to study the effects of Delta Sleep Inducing Peptide-DSIP- on burying behavior 01 rats with diverse stress-sensitivity. Methods: Firstly the correlation between aversive behavior features and somatic stress sensitivity In Wistar rats were studied. The aversive behavior was examine in electric-probe burying response model. when alter slight electric event (0.8-1.4 mAl In grid-floor cage the duration of exploration and freezing behavior, and the individual type of aversive strategy (active type - locomotor behavior. passive type - freezing reaction) were recorded for each rat. Then rats were submitted to 5-days stress session. The obtained data were evaluated by correlation analysis. The second aim was to check the effects of I.p. Injected DSIP (60 nMlkg) on behavioral characteristics raflected stress-sensitivity in Wlstar rats within the same behavior model. Results: The sUbjects with PBSSlve aversive stretegy and long freeZing duretion had a highest stress-sensitivity, and DSIP Improved their burying behavior. Contrary. In others the deficit of burying under the DSIP Influence was lound. Therefore. we conclude that effects of DSIP on aversive behavior In rats and their stress-sensitivity are linked.