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Lactate dehydrogenase isoenzymes in lymphocytes of schizophrenic and alcoholic patients
SIOL. PSYCHIAmy
SerotOllin I
31 yeartI and 72% of them were men. Only 13% visited the GP for the first lime and 82% had previously followed a substitution treatment
wei
(/neltI8dOIl8 or others non registered treatment conceming substitution such .. tJuPr800rPhine 0.2 mg, morphine sulfate, dext~xyphene ..•). At n;tusiOn. 14% of patients received a daily dOSage of buprenorphine <4 mg, 31'% (4-8 mol. 42% (8-t6 mg). 11% [1&-24 mg)and 2"10 ~24 mg. For 74% d patients. the prescription mentioned a pharmacist delivery for a week or ... \tIaI1 a week. The 6 months folloW-Up results will be presented (data will be available In February 1997 for the latest included patients at the end of JlIY 1996).
[61.~ Laet8te dehydrogenase Isoenzymes In lymphocytes of schizophrenic and alcoholic patients
A.L ZhankoV, 5.5. Terovsky. M.V. Kuskov. VA Trtarenko. Mental Health R8s6IJfCh Institute, Sosnovy Bor. Tomsic, 634014, Russia AIm. Investigation of chlorpromazine (CHP. calmodulin inhibitor) and sodium lulfate (SOS) Influence on lactate dehydrogenase (LOG) isoen· zymes actfvity In peripheral blood lymphocytes of healthy subjects (N .. 6) and patientS with schizophrenIa (N .. 10) and alcoholism (N .. 8). Methods: Isolated lymphocytes were treated as follows: 1. solubilized (for 15 min.) In 0.02-0.1% SOS or 2. Incubated (1-2.5 h) in MEM containing CHP (SO jlM) and than destroyed by vortex In hypotonic conditions. Such . aamples were separated by gel electrophoresis. "':'Ulta. In all untreated cells four Isoforms LOH-1-lDH-4 were de• termined- In contrOls SOS reduction of enzymatic activity were gradually raeasect from LOH-1 to LOH-4. In alcoholic patients LOG-4, LOG-3 were more whereas LOH-1 less resistant to SOS action than In healthy subjects. of schiZophrenic patients have sufficientiy higher susceptibility t:) ~ The CHP effect on Intact cells wes similar the direct SOS HIuenC8 and deP9flded upon Incubation time. ConClusion. Thus, testing of secondary messenger system and metabOlism of lymphocytes may be useful In understanding of immune • rment formation In patients with different psychiatric disorders.
dodeCYI
", .dorms
62. Serotonin I
@_jJ
Midbrain and hippocampal 5-HT1A receptors In the SHR and Lewis rat strains that differ In anxiety tests
f. O\aOUloff. O. Berton, A. Kullkov, A. Ramos, S. Aguerre, P. Monmade. du Stress. INSERM CJF 94-05, Bordeaux, Francs
GMetiq1J6
~ goal was (I) to select among six rats strains (namely SHR. Lewis, Brown• WI&t8I' Kyoto. Fischer 344, and W1star Furth) those differing the
:.a
,,":,~itioned models of anxiety, (ii) to compare these strains for both (mlc:lbI'lli n) and postsynaptic (hippocampus) 5-HT1A receptors (which ~ anxiety-related behaviours). and (iii) to analyse the effects of two Ilre$SOf'S on anxiety and/or 5-HT1Areceptors In the two strains. When tested In an open field. an elevated plus-m~e, and a blacklwhite box, the SHR l1li and the Lewis rats were respectively the least and the most anxious strainS • difference which was sex-Independent Midbrain or hippocam• pus r~roxy-2-(di-n-propylamjno)tetralin «('Hj8-OH-OPAT) binding at 5-HT recePtors. and 8-OH-DPAT-elielted Inhibition of 5-HT synthesis In ~ (an index of 5-HT1A autoreceptor activity) were strain-independent ~ 8-OH-DPAT-Induced forepaw treading and flat body posture were ~ hlghel' and lower In SHR rats, compared to Lewis rats. Fasting 4 h affected neither midbrain ('H18-0H-DPAT binding nor 8-oH·OPAT• ~ Inhibition of 5-HT synthesis In both streins. On repeated exposure to soc;iaI streSS (defeat and Isolation), hippocampal 5-HT1A receptors were esec:reased in both strains, a change associated with Increased anxiety In the eIevalSd p1us-maze and Increased Immobility In the forced swimming test In Uwia rats only.
1997;42:Is-ms
162-21
159S
5HT-moduJlne regUlates 5HT1B receptor activity In rat In stress situations
G. Fillion, L SegUin, J.e. Seznec, P. Uscla, O. Massot, J.e. Rousselle, B. Grimaldi, M.P. Fillion, C.Y. Guezennec. Pharmacologie neuro/mmunoendocrinienne, Institut Pasteur, Paris, Fraf1C8 5HT18 receptors controls the serotoninerglc activity as auto and heterore• ceptors. 5HT-moduline, a recently isolated endogenous peptide (Rousselle et aI., 1996) specifically Interact with 5HT1e receptors (Massot et aI., 1996). We studied the possible involvement of 5HT,e receptors In stress situations. Methods: The sensitivity of 5HT1B receptors was determlned by measur• ing the Inhibitory activity of a 5HT18 agonist on the production of cAMP In substantia nigra. Results: Acute restraint stress shifted to the right the dose-response curve of CP 93129. It was also shown that rats trained to run for 5 weeks either moderately (one hour per day at 18 mlmin) or Intensively (120 min per day at 30 mlmln with a 7% grade) exhibited a similar desensitization of their 5HT B receptors; an additional restraint stress, did not Induce any ' of 5HT'B receptors in the moderate running rats whereas further change rats running Intensively exhibited a further desensitization of the receptors. 5HT-moduline was shown to be present In rat cerebrospinal fluid and lev inj~ons of 5HT-moduline mimiked the effect of stress on 5HT'B receptor activity. In conclusion. stress situations alter the activity of the serotonlnerglc sys• tem via modifications of SHT1B receptor activity. 5HT-moduline presumably plays a crucial role in these effects and potentially represents an Impor· tant agent in adeptative mechanisms and might be Involved In pathological psychiatry related to serotonlnergIc disorders.
162-31
Effects of prenatal stress combined wltlh Ipsaplrone or diazepam treatments on central 5-HT, Band 5-HT2 receptor binding In rat offspring
F. H6ry, A. Semont, P. Boulenguez, M. Faudon, P. Siaud, M.P. Fache• INSERM U297, Institut Ft5d8ratif Jeen Roche, Faculfe de M9dec1ne, Bd Pierre Dramard, 13916 Marseille Cedex 20, France A large body of data show that 5-HT Is Involved In brain development. We preViously demonstrated the role of somatodendritic 5-HT release and 5-HTIA autoreceptors In regulating 5-HT release (Becquet et aI. 1990, Neurosci. 39: 638). The goal of this study was to delenmlne 1) If autoregulatory mechanisms via 5-HT,A appear very early during brain embryonic development and to analyze 2) the effects Induced by a new class of anxlolytics (5-HT1A agonlsts) administered to pregnant stressed rats on the 5-HT systems In offspring. 8-oH-DPAT binding on 5-HTIA Is detected as soon BS 14tl1 gestation day (GO) In raphe nuclei. However, autoregUlation of 5-HT (K+) evoked release Induced by 8-oH·OPAT was only observed from the 17th GO. Prenatal stress (vehicle injection .. sham group) from 91n to 20th GO induced a decrease of 5-HT,8 and 5-HT2AI2C receptors density In cerebral cortex of rat offspring from 1to 90 days associated with an Increase of 5-HIAA/5-HT ratio, compared to sham group. Chronic Ipsaplrone (10 mg/kg) and diazepam (5 mg/kg) treatments to pregnant rets induced a penmanent Increase of 5-HT18 and 5-HT2AI2C receptors. However, no statistical differences were observed between offspring from unstressed (control) and stressed anxiolytic treated rats. These data confinm the functional role of 5-HT1A In autoregulatory mech· anisms during early period of development and show that prenatal stress Induced-effects on SHT systems were counteracted by anxiolytic prenatal treatments.
162-41
Platelet serotonerglc functions and light therapy In SAD
Rigmor Stain-Malmgren, Bengl F. Kjellman, Anna Aberg-Wlstedt. Karolinska Institute. Institution of Clinical Neuroscience. Dept. of PsychIatry, St. G(}ran's Hospital, S-112 8t, Stockholm. Sweden We have investigated the effect of light therapy In 16 patients with d0c• umented SAO on platelet 14c-serotonin uptake and 3H-paroxetine and 3H-LSD-blnding to platelet membranes. The light therapy was applied 07.00-00.00 AM for ten consecutive days In a special room, where in• direct full-spectrum light was reflected will! a luminance of 350 candelalm2 . The degree of depression was rated before and after light therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline bio-
SerotOllin I
31 yeartI and 72% of them were men. Only 13% visited the GP for the first lime and 82% had previously followed a substitution treatment
wei
(/neltI8dOIl8 or others non registered treatment conceming substitution such .. tJuPr800rPhine 0.2 mg, morphine sulfate, dext~xyphene ..•). At n;tusiOn. 14% of patients received a daily dOSage of buprenorphine <4 mg, 31'% (4-8 mol. 42% (8-t6 mg). 11% [1&-24 mg)and 2"10 ~24 mg. For 74% d patients. the prescription mentioned a pharmacist delivery for a week or ... \tIaI1 a week. The 6 months folloW-Up results will be presented (data will be available In February 1997 for the latest included patients at the end of JlIY 1996).
[61.~ Laet8te dehydrogenase Isoenzymes In lymphocytes of schizophrenic and alcoholic patients
A.L ZhankoV, 5.5. Terovsky. M.V. Kuskov. VA Trtarenko. Mental Health R8s6IJfCh Institute, Sosnovy Bor. Tomsic, 634014, Russia AIm. Investigation of chlorpromazine (CHP. calmodulin inhibitor) and sodium lulfate (SOS) Influence on lactate dehydrogenase (LOG) isoen· zymes actfvity In peripheral blood lymphocytes of healthy subjects (N .. 6) and patientS with schizophrenIa (N .. 10) and alcoholism (N .. 8). Methods: Isolated lymphocytes were treated as follows: 1. solubilized (for 15 min.) In 0.02-0.1% SOS or 2. Incubated (1-2.5 h) in MEM containing CHP (SO jlM) and than destroyed by vortex In hypotonic conditions. Such . aamples were separated by gel electrophoresis. "':'Ulta. In all untreated cells four Isoforms LOH-1-lDH-4 were de• termined- In contrOls SOS reduction of enzymatic activity were gradually raeasect from LOH-1 to LOH-4. In alcoholic patients LOG-4, LOG-3 were more whereas LOH-1 less resistant to SOS action than In healthy subjects. of schiZophrenic patients have sufficientiy higher susceptibility t:) ~ The CHP effect on Intact cells wes similar the direct SOS HIuenC8 and deP9flded upon Incubation time. ConClusion. Thus, testing of secondary messenger system and metabOlism of lymphocytes may be useful In understanding of immune • rment formation In patients with different psychiatric disorders.
dodeCYI
", .dorms
62. Serotonin I
@_jJ
Midbrain and hippocampal 5-HT1A receptors In the SHR and Lewis rat strains that differ In anxiety tests
f. O\aOUloff. O. Berton, A. Kullkov, A. Ramos, S. Aguerre, P. Monmade. du Stress. INSERM CJF 94-05, Bordeaux, Francs
GMetiq1J6
~ goal was (I) to select among six rats strains (namely SHR. Lewis, Brown• WI&t8I' Kyoto. Fischer 344, and W1star Furth) those differing the
:.a
,,":,~itioned models of anxiety, (ii) to compare these strains for both (mlc:lbI'lli n) and postsynaptic (hippocampus) 5-HT1A receptors (which ~ anxiety-related behaviours). and (iii) to analyse the effects of two Ilre$SOf'S on anxiety and/or 5-HT1Areceptors In the two strains. When tested In an open field. an elevated plus-m~e, and a blacklwhite box, the SHR l1li and the Lewis rats were respectively the least and the most anxious strainS • difference which was sex-Independent Midbrain or hippocam• pus r~roxy-2-(di-n-propylamjno)tetralin «('Hj8-OH-OPAT) binding at 5-HT recePtors. and 8-OH-DPAT-elielted Inhibition of 5-HT synthesis In ~ (an index of 5-HT1A autoreceptor activity) were strain-independent ~ 8-OH-DPAT-Induced forepaw treading and flat body posture were ~ hlghel' and lower In SHR rats, compared to Lewis rats. Fasting 4 h affected neither midbrain ('H18-0H-DPAT binding nor 8-oH·OPAT• ~ Inhibition of 5-HT synthesis In both streins. On repeated exposure to soc;iaI streSS (defeat and Isolation), hippocampal 5-HT1A receptors were esec:reased in both strains, a change associated with Increased anxiety In the eIevalSd p1us-maze and Increased Immobility In the forced swimming test In Uwia rats only.
1997;42:Is-ms
162-21
159S
5HT-moduJlne regUlates 5HT1B receptor activity In rat In stress situations
G. Fillion, L SegUin, J.e. Seznec, P. Uscla, O. Massot, J.e. Rousselle, B. Grimaldi, M.P. Fillion, C.Y. Guezennec. Pharmacologie neuro/mmunoendocrinienne, Institut Pasteur, Paris, Fraf1C8 5HT18 receptors controls the serotoninerglc activity as auto and heterore• ceptors. 5HT-moduline, a recently isolated endogenous peptide (Rousselle et aI., 1996) specifically Interact with 5HT1e receptors (Massot et aI., 1996). We studied the possible involvement of 5HT,e receptors In stress situations. Methods: The sensitivity of 5HT1B receptors was determlned by measur• ing the Inhibitory activity of a 5HT18 agonist on the production of cAMP In substantia nigra. Results: Acute restraint stress shifted to the right the dose-response curve of CP 93129. It was also shown that rats trained to run for 5 weeks either moderately (one hour per day at 18 mlmin) or Intensively (120 min per day at 30 mlmln with a 7% grade) exhibited a similar desensitization of their 5HT B receptors; an additional restraint stress, did not Induce any ' of 5HT'B receptors in the moderate running rats whereas further change rats running Intensively exhibited a further desensitization of the receptors. 5HT-moduline was shown to be present In rat cerebrospinal fluid and lev inj~ons of 5HT-moduline mimiked the effect of stress on 5HT'B receptor activity. In conclusion. stress situations alter the activity of the serotonlnerglc sys• tem via modifications of SHT1B receptor activity. 5HT-moduline presumably plays a crucial role in these effects and potentially represents an Impor· tant agent in adeptative mechanisms and might be Involved In pathological psychiatry related to serotonlnergIc disorders.
162-31
Effects of prenatal stress combined wltlh Ipsaplrone or diazepam treatments on central 5-HT, Band 5-HT2 receptor binding In rat offspring
F. H6ry, A. Semont, P. Boulenguez, M. Faudon, P. Siaud, M.P. Fache• INSERM U297, Institut Ft5d8ratif Jeen Roche, Faculfe de M9dec1ne, Bd Pierre Dramard, 13916 Marseille Cedex 20, France A large body of data show that 5-HT Is Involved In brain development. We preViously demonstrated the role of somatodendritic 5-HT release and 5-HTIA autoreceptors In regulating 5-HT release (Becquet et aI. 1990, Neurosci. 39: 638). The goal of this study was to delenmlne 1) If autoregulatory mechanisms via 5-HT,A appear very early during brain embryonic development and to analyze 2) the effects Induced by a new class of anxlolytics (5-HT1A agonlsts) administered to pregnant stressed rats on the 5-HT systems In offspring. 8-oH-DPAT binding on 5-HTIA Is detected as soon BS 14tl1 gestation day (GO) In raphe nuclei. However, autoregUlation of 5-HT (K+) evoked release Induced by 8-oH·OPAT was only observed from the 17th GO. Prenatal stress (vehicle injection .. sham group) from 91n to 20th GO induced a decrease of 5-HT,8 and 5-HT2AI2C receptors density In cerebral cortex of rat offspring from 1to 90 days associated with an Increase of 5-HIAA/5-HT ratio, compared to sham group. Chronic Ipsaplrone (10 mg/kg) and diazepam (5 mg/kg) treatments to pregnant rets induced a penmanent Increase of 5-HT18 and 5-HT2AI2C receptors. However, no statistical differences were observed between offspring from unstressed (control) and stressed anxiolytic treated rats. These data confinm the functional role of 5-HT1A In autoregulatory mech· anisms during early period of development and show that prenatal stress Induced-effects on SHT systems were counteracted by anxiolytic prenatal treatments.
162-41
Platelet serotonerglc functions and light therapy In SAD
Rigmor Stain-Malmgren, Bengl F. Kjellman, Anna Aberg-Wlstedt. Karolinska Institute. Institution of Clinical Neuroscience. Dept. of PsychIatry, St. G(}ran's Hospital, S-112 8t, Stockholm. Sweden We have investigated the effect of light therapy In 16 patients with d0c• umented SAO on platelet 14c-serotonin uptake and 3H-paroxetine and 3H-LSD-blnding to platelet membranes. The light therapy was applied 07.00-00.00 AM for ten consecutive days In a special room, where in• direct full-spectrum light was reflected will! a luminance of 350 candelalm2 . The degree of depression was rated before and after light therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline bio-