MODULATION OF 5-HT AND GABA RECEPTORS BY PSYCHOACTIVE DRUGS
Main researcher
: PERIČIĆ, DANKA (36151) Assistants
TVRDEIĆ, ANTE (157335)
MUCK-ŠELER, DOROTEA (32626)
PIVAC, NELA (113176)
BJEGOVIĆ, MILICA (3905)
CIK, MIROSLAV (180024)
BUJAS, MAJA (900524)
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
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
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 Other information about the project.