SVIBOR - Project code: 1-08-173

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

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Project code: 1-08-173


MODULATION OF 5-HT AND GABA RECEPTORS BY PSYCHOACTIVE DRUGS


Main researcher: PERIČIĆ, DANKA (36151)



Assistants
Type of research: basic
Duration from: 01/01/91. to 12/31/95.

Papers on project (total): 64
Papers on project quoted in Current Contents: 20
Institution name: Institut "Ruđer Bošković", Zagreb (98)
Department/Institute: Department of Experimental Biology and Medicine Laboratory for Molecular Neuropharmacology
Address: Institut "Ruđer Bošković", Bijenička 54, P.P. 1016
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)4561126
Fax: 385 (0)425497
E-mail: PERICIC¦OLIMP.IRB.HR

Summary: The interaction of known (antidepressants, anxiolytics) andpotential neuropsychoactive drugs (especially of the potentialantidepressant dihydroergosine) and of the specific ligandswith GABA-A and 5-HT-1 receptors will be investigated. Thespecial emphasis will be given to species differences in thestructural and functional properties of the subunits of theGABA-A receptor complex. In these studies we are going to applythe methods of radioligand binding to the synaptosomal membranesisolated from the brain of different species (mouse, rat, cow,man), and the methods from molecular genetics of eukaryots whichwill be introduced for this purpose, as well as for the purposeof the investigation of more subtile mechanisms ofneurotransmission. In parallel, by means of the behaviouralmethods the anxiolytic and anticonvulsive properties of thepotential neuropsychoactive drugs will be studied, and by thefluorimetric and radioimmunochemical methods the mechanism ofaction of the known anxiolytic drug dioazepam on the activity ofthe hypothalamo-pituitary-adrenal axis will be investigated. Indepressed patients treated with dihydroergosine and otherantidepressants the concentration of GABA in plasma and of 5-HTin platelets will be determined.

Keywords: GABA-A RECEPTORS, 5-HT-1 RECEPTORS, NEUROPSYCHOPHARMACA, ERGOT ALKALOIDS, DIAZEPAM, LIGAND-RECEPTOR BINDING METHODS, BEHAVIOURAL METHODS, SEX DIFFERENCES, SPECIES DIFFERENCES, 5-HT IN PLATELETS, HYPOTHALAMO-PITUITARY-ADRENAL AXIS

Research goals: 1. Compare the functional properties of GABA-A receptor complex in several species including man 2. Study the regional distribution of species differences in GABA-A receptor complex 3. Elucidate the molecular mechanism of action of some antidepressants on the Cl channel, part of GABA-A receptor complex. 4. Find out whether dihydroergosine possesses anxiolytic and anticonvulsive properties 5. Introduce the methods from the molecular genetic of eukaryots in order to study the more subtile molecular mechanisms of neurotransmission 6. Study the interaction between some potential and classic antidepressants and 5-HT-1 receptors isolated from the rat, bovine and human brain 7. Determine the concentration of GABA in plasma and 5-HT in platelets of depressive patients treated with dihydroergosine and some other antidepressants 8. Elucidate the mechanism of action of diazepam on the hypothalamo-pituitary-adrenal axis


COOPERATION - INSTITUTIONS


  1. Name of institution: Psihijatrijska klinika, Klinički bolnički centar Rebro
    Type of institution: University/Faculty
    Type of cooperation: Joint publishing of scientific papers
    City: 10000 - Zagreb, Croatia

  2. Name of institution: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University
    Type of institution: University/Faculty
    Type of cooperation: Joint publishing of scientific papers
    City: Montreal, Canada, PQ

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Last update: 10/13/95
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