Research

Cannabinoids and synaptic transmission
The Gα_i/o protein-coupled CB₁ cannabinoid receptor is the primary neuronal target of the phytocannabinoid Δ⁹-tetrahydrocannabinol. It can also be activated by the endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonylglycerol. The CB₁ receptor is widely distributed in the central nervous system. The aim of our group is to analyse the effects of exogenous and endogenous cannabinoids on synaptic transmission between identified neurons in the central nervous system. The figure below shows an example for modulation of synaptic transmission by cannabinoids. For review see Szabo and Schlicker, Handb Exper Pharmacol 168: 327-365, 2005.

Cannabinoids inhibit GABAergic synaptic transmission between basket and Purkinje cells in the cerebellar cortex. Brain slices were prepared from rat cerebellum. Spontaneously occurring action potentials (APs) in presynaptic basket cells and GABAergic inhibitory postsynaptic currents (sIPSCs) in postsynaptic Purkinje cells were recorded with the patch-clamp technique. During the initial reference period (PRE), every presynaptic AP was followed by a postsynaptic sIPSC. The synthetic CB₁ cannabinoid receptor agonist WIN55212-2 inhibits synaptic transmission: now, several presynaptic action potentials are not followed by postsynaptic sIPSCs (the stars indicate these “synaptic failures”).

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Publications

I.	Originalarbeiten
69.	Hermanns-Clausen M, Kneisel S, Hutter M, Szabo B, Auwärter V (2013) Acute intoxication by synthetic cannabinoids - Four case reports. Drug Testing and Analysis DOI: 10.1002/dta.1483
68.	Simon AC, Loverdo C, Gaffur A-L, Urbanski M, Carrel D, Rival I, Leterrier C, Benichou O, Dournaud P, Szabo B, Voituriez R, Lenkei Z (2013) Activation-dependent plasticity of polarized GPCR distribution on the neuronal surface. J Molec Cell Biol 5: 250–265
67.	Hermanns-Clausen M, Kneisel S, Szabo B, Auwärter V (2012) Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 108: 534–544
66.	Kovacs FE, Knop T, Urbanski MJ, Freiman I, Freiman TM, Feuerstein TJ, Zentner J, Szabo B (2012) Exogenous and endogenous cannabinoids suppress inhibitory neurotransmission in the human neocortex. Neuropsychopharmacology 37: 1104–1114
65.	Kovacs FE, Illes P, Szabo B (2011) Purinergic receptor-mediated endocannabinoid production and retrograde synaptic signaling in the cerebellar cortex. Brit J Pharmacol 162: 974–988
64.	Urbanski MJ, Kovacs FE, Szabo B (2010) Endocannabinoid-mediated synaptically evoked suppression of GABAergic transmission in the cerebellar cortex. Neuroscience 169: 1268-1278
63.	Beetz N, Harrison MD, Brede M, Zong X, Urbanski MJ, Sietmann A, Kaufling J, Barrot M, Seeliger MW, Vieira-Coelho MA, Hamet P, Gaudet D, Seda O, Tremblay J, Kotchen TA, Kaldunski M, Nüsing R, Szabo B, Jacob HJ, Cowley Jr. AW, Biel M, Stoll M, Lohse MJ, Broeckel U, Hein L (2009) Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice. J Clin Invest 119: 3597-3612.
62.	Urbanski MJ, Kovacs FE, Szabo B (2009) Depolarizing GABAergic synaptic input triggers endocannabinoid-mediated retrograde synaptic signaling. Synapse 63: 643-652.
61.	Gilsbach R, Röser C, Beetz N, Brede M, Hadamek K, Haubold M, Leemhuis J, Philipp M, Schneider J, Urbanski M, Szabo B, Weinshenker D, Hein L (2009) Genetic dissection of α₂-adrenoceptor functions in adrenergic versus non-adrenergic cells. Mol Pharmacol 75: 1160-1170.
60.	Szabo B, Urbanski MJ, Bisogno T, Di Marzo V, Mendiguren A, Bär W and Freiman I (2006) Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol. J Physiol (London) 577: 263-280.
59.	Freiman I, Anton A, Monyer H, Urbanski MJ, Szabo B (2006) Analysis of the effects of cannabinoids on identified synaptic connections in the caudate-putamen by paired recordings in transgenic mice. J Physiol (London) 575: 789-806.
58.	Engler B, Freiman I, Urbanski M, Szabo B (2006) Effects of exogenous and endogenous cannabinoids on GABAergic neurotransmission between the caudate-putamen and the globus pallidus in the mouse. J Pharmacol Exp Ther 316: 608–617.
57.	Freiman I, Szabo B (2005) Cannabinoids depress excitatory neurotransmission between the subthalamic nucleus and the globus pallidus. Neuroscience 133: 305-313.
56.	Pfitzer T, Niederhoffer N, Szabo B (2005) Search for an endogenous cannabinoid-mediated effect in the sympathetic nervous system. Naunyn-Schmiedeberg´s Arch Pharmacol 371: 9-17.
55.	Szabo B, Than M, Wallmichrath I, Thorn D (2004) Analysis of the effects of cannabinoids on synaptic transmission between basket and Purkinje cells in the cerebellar cortex of the rat. J Pharmacol Exp Ther 310: 915-925.
54.	Pfitzer T, Niederhoffer N, Szabo B (2004) Central effects of the cannabinoid receptor agonist WIN55212-2 on respiratory and cardiovascular regulation in anaesthetised rats. Br J Pharmacol 14: 943-952.
53.	Steffens M, Szabo B, Klar M, Rominger A, Zentner J, Feuerstein TJ (2003) Modulation of electrically evoked acetylcholine release through cannabinoid CB1 receptors: Evidence for an endocannabinoid tone in the human neocortex. Neuroscience 120: 455-465.
52.	Schmid K, Niederhoffer N, Szabo B (2003) Analysis of the respiratory effects of cannabinoids in rats. Naunyn-Schmiedeberg´s Arch Pharmacol 368: 301-308.
51.	Niederhoffer N, Schmid K, B Szabo (2003) The peripheral sympathetic nervous system is the major target of cannabinoids at eliciting cardiovascular depression. Naunyn-Schmiedeberg´s Arch Pharmacol 367: 434-443.
50.	Vagts DA, Iber T, Puccini M, Szabo B, Haberstroh J, Villinger F, Geiger K, Nöldge-Schomburg GFE (2003) The effects of thoracic epidural anesthesia on hepatic perfusion and oxygenation in healthy pigs during general anesthesia and surgical stress. Anesth Analg 97: 1824-1832.
49.	Vagts DA, Iber T, Szabo B, Haberstroh J, Reising K, Puccini M, Geiger K, Nöldge-Schomburg GFE (2003) Effects of epidural anaesthesia on intestinal oxygenation. Br J Anaesth 90: 212-220.
48.	Szabo B, Siemes S, Wallmichrath I (2002) Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. Eur J Neurosci 15: 2057-2061.
47.	Wallmichrath I, Szabo B (2002) Cannabinoids inhibit striatonigral GABAergic neurotransmission in the mouse. Neuroscience 113: 671-682.
46.	Than M, Szabo B (2002) Analysis of the function of GABAB receptors on inhibitory afferent neurons of Purkinje cells in the cerebellar cortex of the rat. Eur J Neurosci 15: 1575-1584.
45.	Wallmichrath I, Szabo B (2002) Analysis of the effect of cannabinoids on GABAergic neurotransmission in the substantia nigra pars reticulata. Naunyn-Schmiedeberg´s Arch Pharmacol 365, 326-334.
44.	Szabo B, Fritz T, Wedzony K (2001) Effects of imidazoline antihypertensive drugs on sympathetic tone and noradrenaline release in the prefrontal cortex. Br J Pharmacol 134: 295-304
43.	Niederhoffer N, Hansen HH, Fernandez-Ruiz JJ, Szabo B (2001) Effects of cannabinoids on adrenaline release from adrenal medullary cells. Br J Pharmacol 134: 1319-1327.
42.	Szabo B, Nordheim U, Niederhoffer N (2001) Effects of cannabinoids on sympathetic and parasympathetic neuro-effector transmission in the rabbit heart. J Pharmacol Exp Ther 297: 819-826.
41.	Niederhoffer N, Szabo B (2000) Cannabinoids cause central sympathoexcitation and bradycardia in rabbits. J Pharmacol Exp Ther 294: 707-713.
40.	Szabo B, Wallmichrath I, Mathonia P, Pfreundtner C (2000) Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata. Neuroscience 97: 89-97.
39.	Szabo B, Müller T, Koch H (1999) Effects of cannabinoids on dopamine release in the corpus striatum and the nucleus accumbens in vitro. J Neurochem 73: 1084-1089.
38.	Bock C, Niederhoffer N, Szabo B (1999) Analysis of the receptor involved in the central hypotensive effect of rilmenidine and moxonidine. Naunyn-Schmiedeberg´s Arch Pharmacol 359: 262-271
37.	Niederhoffer N, Szabo B (1999) Involvement of CB1 cannabinoid receptors in the EDHF-dependent vasorelaxation in rabbits. Br J Pharmacol 126: 1383-1386
36.	Niederhoffer N, Szabo B (1999) Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic cardiovascular regulation. Br J Pharmacol 126: 457-466
35.	Szabo B, Bock C, Nordheim N, Niederhoffer N (1999) Mechanism of the sympathoinhibition produced by the clonidine-like drugs rilmenidine and moxonidine. Ann New York Acad Sci 881: 253-264
34.	Szabo B, Dörner L, Pfreundtner C, Nörenberg W, Starke K (1998) Inhibition of GABAergic inhibitory postsynaptic currents by cannabinoids in rat corpus striatum. Neuroscience 85: 395-403.
33.	Nörenberg W, Schöffel E, Szabo B, Starke K (1997) Subtype determination of soma-dendritic a2-autoreceptors in slices of rat locus coeruleus. Naunyn-Schmiedeberg´s Arch Pharmacol 356: 159-165
32.	Szabo B, Urban R (1997) Role of I1 imidazoline receptors in the sympathoinhibition produced by intracisternally administered rilmenidine and moxonidine. Drug Res 47 (II): 1009-1015
31.	Szabo B, Fröhlich R, Illes P (1996) No evidence for functional imidazoline receptors on locus coeruleus neurons. Naunyn-Schmiedeberg´s Arch Pharmacol 353: 557-563
30.	Driessen B, Concalves J, Szabo B (1996) Failure of tyramine to release neuronal ATP as a cotransmitter of noradrenaline in the guinea-pig vas deferens. Naunyn-Schmiedeberg´s Arch Pharmacol 353: 175-183
29.	Szabo B, Urban R (1995) Mechanism of sympathoinhibition by imidazolines. Ann New York Acad Sci 763: 552-565
28.	Urban R, Szabo B, Starke K (1995) Involvement of peripheral presynaptic inhibition in the reduction of sympathetic tone by moxonidine, rilmenidine and UK 14304. Eur J Pharmacol 282: 29-37
27.	Urban R, Szabo B, Starke K (1995) Involvement of a2-adrenoceptors in the cardiovascular effects of moxonidine. Eur J Pharmacol 282: 19-28
26.	Cassel JC, Jeltsch H, Neufang B, Lauth D, Szabo B, Jackisch R (1995) Downregulation of muscarinic- and 5-HT1B-receptor-mediated modulation of [3H]-acetylcholine release in brain slices of rats with fimbria-fornix lesions and intrahippocampal grafts of septal origin. Brain Res 704: 153-166
25.	Szabo B, Urban R, Starke K (1995) Cardiovascular effects of agmatine, a "clonidine-displacing substance", in conscious rabbits. Naunyn-Schmiedeberg´s Arch Pharmacol 351: 268-273
24.	Szabo B, Obergfell A, Starke K (1995) Involvement of monoamine uptake inhibition and local anesthesia in the cardiovascular response to cocaine in conscious rabbits. J Pharmacol Exp Ther 273: 128-137
23.	Urban R, Szabo B, Starke K (1994) Is the sympathoinhibitory effect of rilmenidine mediated by alpha-2 adrenoceptors or imidazoline receptors? J Pharmacol Exp Ther 270: 572-578
22.	Szabo B, Urban R, Starke K (1993) Sympathoinhibition by rilmenidine in conscious rabbits: involvement of a2-adrenoceptors. Naunyn-Schmiedeberg´s Arch Pharmacol 348: 593-600
21.	Szabo B, Auberle T, Starke K (1993) Inhibition of uptake1 by (+)-oxaprotiline reveals a differential central regulation of noradrenaline and adrenaline release. Naunyn-Schmiedeberg´s Arch Pharmacol 348: 249-257
20.	Bültman R, Szabo B, Starke K (1993) Inhibition by ethanol of contractions of rat vas deferens: no evidence for selective blockade of P2x-purinoceptors. Naunyn-Schmiedeberg´s Arch Pharmacol 347: 527-533
19.	Szabo B, Schramm A, Starke K (1992) Effect of yohimbine on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits. J Pharmacol Exp Ther 260: 780-788
18.	Szabo B, Karsch V, Starke K (1992) Effects of inhibitors of neuronal uptake of 5-HT on sympathetic cardiovascular regulation. J Cardiovasc Pharmacol 20: 99-107
17.	Szabo B, Crass D, Starke K (1992) Effect of the dopamine D2 receptor agonist quinpirole on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits. J Pharmacol Exp Ther 263: 806-815
16.	Szabo B, Schultheiss A, Starke K (1991) The noradrenaline uptake inhibitor, (+)-oxaprotiline, but not the inactive enantiomer, (-)-oxaprotiline, inhibits sympathetic nerve activity in the rabbit: involvement of adrenoceptors. Eur J Pharmacol 199: 325-334
15.	Meyer DK, Holland A, Lais A, Szabo B (1991) Effects of p-chloroamphetamine on release of [3H]gamma-aminobutyric acid from slices of rat caudate-putamen. Eur J Pharmacol 196: 189-195
14.	Szabo B, Schultheiss A (1990) Desipramine inhibits sympathetic nerve activity in the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 342: 469-476
13.	Szabo B, Hedler L, Schurr C, Starke K (1990) Peripheral presynaptic facilitatory effect of angiotensin II on noradrenaline release in anesthetized rabbits. J Cardiovasc Pharmacol 15: 968-975
12.	Szabo B, Hedler L, Starke K (1989) Facilitation of the release of noradrenaline: an extraadrenal effect of adrenocorticotropic hormone. Resuscitation 18: 229-242
11.	Szabo B, Hedler L, Starke K (1989) Peripheral presynaptic and central effects of clonidine, yohimbine and rauwolscine on the sympathetic nervous system in rabbits. Naunyn-Schmiedeberg's Arch Pharmacol 340: 648-657
10.	Szabo B, Hedler L, Schurr C, Starke K (1988) Peripheral sympatho-inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits. Br J Pharmacol 94: 781-788
9.	Szabo B, Hedler L, Schurr C, Starke K (1988) ACTH increases nordrenaline release in the rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 338: 368-372
8.	Szabo B, Wichmann T, Starke K (1987) Presynaptic opioid receptors in the portal vein of the rabbit. Eur J Pharmacol 139: 103-110
7.	Szabo B, Hedler L, Lichtwald K, Starke K (1987) ACTH increases noradrenaline release in pithed rabbits with electrically stimulated sympathetic outflow. Eur J Pharmacol 136: 391-399
6.	Acs Zs, Szabo B, Kapocs G, Makara GB (1987) g-Aminobutyric acid stimulates pituitary growth hormone secretion in the neonatal rat. A superfusion study. Endocrinology 120: 1790-1798
5.	Szabo B, Hedler L, Starke K (1986) Dopamine receptor agonist and alpha-2 adrenoceptor antagonist effects of fenoldopam in rabbits. J Pharmacol Exp Ther 239: 881-886
4.	Szabo B, Hedler L, Ensinger H, Starke K (1986) Opioid peptides decrease noradrenaline release and blood pressure in the rabbit at peripheral receptors. Naunyn-Schmiedeberg's Arch Pharmacol 332: 50-56
3.	Ensinger H, Hedler L, Szabo B, Starke K (1986) Bremazocine causes sympatho-inhibition and hypotension in rabbits by activating peripheral k-receptors. J Cardiovasc Pharmacol 8: 470-475
2.	Enyedi P, Szabo B, Spät A (1985) Reduced responsiveness of glomerulosa cells after prolonged stimulation with angiotensin II. Am J Physiol 248: E209-E214
1.	Enyedi P, Szabo B, Spät A (1983) Failure of vasoactive intestinal polypeptide to stimulate aldosterone production. Acta Physiol Hung 61: 77-79
II.	Übersichtsartikel
4.	Szabo B, Schlicker E (2005) Effects of cannabinoids on neurotransmission. In: Pertwee RG (Ed.) Cannabinoids, Handbook of Experimental Pharmacology, Vol. 168, pp 327-365, Springer, Berlin.
3.	Wallmichrath I, Szabo B (2004) Cannabinoide und neuronale Signalübertragung. Sucht 50: 297-308.
2.	Szabo B (2002) Imidazoline antihypertensive drugs - a critical review on their mechanism of action. Pharmacol Ther 93: 1-35.
1.	Szabo B, Niederhoffer N (1998) Effects of cannabinoids on cardiovascular regulation in rabbits. Pharmacol Toxicol 83 (suppl. I): 87-89
III.	Buchbeiträge
8.	Wallmichrath I, Szabo B (2004) Influence of exogenous and endogenous cannabinoids on synaptic transmission. In: Wenger T (Ed.) Recent advances in pharmacology and physiology of cannabinoids, pp.75-96. Research Signpost, Kerala
7.	Szabo B, Wallmichrath I (2003) Cannabinoide und die Kommunikation zwischen Neuronen. In: Fischer J (Ed.) Weggefährten, pp. 218-249. Pabst Science Publishers, Berlin
6.	Szabo B, Wallmichrath I, Niederhoffer N (2002) Wirkungen von Cannabinoiden auf Neurone. In: Richter G, Rommelspacher H, Spies C (Eds.) "Alkohol, Nikotin, Kokain... und kein Ende?", pp. 387-394. Pabst Science Publishers, Berlin
5.	Szabo B (2002) A szimpatikus idegrendszer gyógyszeres befolyásolása (auf Deutsch: Pharmakologische Beeinflussung des sympathischen Nervensystems). In: Vizi E-Sz (Ed.) Humán farmakológia: a racionális gyógyszerterápia alapjai (auf Deutsch: Humanpharmakologie: Grundlagen der rationalen Pharmakotherapie), pp. 440-452. Medicina, Budapest
4.	Schultheiss A, Szabo B, Starke K (1991) Inhibition of NA uptake by (+)-oxaprotiline inhibits sympathetic nerve activity. In: Langer SZ, Galzin AM, Costentin J (Eds.) Advances in the biosciences, Presynaptic receptors and neuronal transporters, Vol. 82, pp. 327-328. Pergamon, Oxford
3.	Szabo B, Ramme D, Starke K (1988) Opioid receptors in the sympathetic supply to blood vessels and the heart. In: Stumpe KO, Kraft K, Faden AI (Eds.) Opioid peptides and blood pressure control, pp. 129-140. Springer, Berlin
2.	Starke K, Illes P, Ramme D, Ensinger H, Hedler L, Szabo B, von Kügelgen I, Pfeiffer N, Limberger N (1987) Peripheral pre-junctional opioid receptors in cardiovascular control. In: Nobin A, Owman C, Arneklo-Nobin B (Eds.) Neuronal messengers in vascular function, pp. 247-269. Elsevier, Amsterdam
1.	Starke K, Majewski H, Ensinger H, Szabo B, Hedler L (1986) In vivo operation of prejunctional adrenoceptors in the peripheral sympathetic nervous system. In: Grobecker H, Philippu A, Starke K (Eds.) New aspects of the role of adrenoceptors in the cardiovascular system, pp. 43-56. Springer, Berlin

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Members of the group

Bela Szabo
Ilka Freiman
Flora Kovacs, Mario Lederer, Sophia Linder, Holger Schwarz, Tim Knop, Marco Spehl
Previous: Michal Urbanski, Wolfram Bär

Professor Dr. med. Bela Szabo

Telefon: +49-761-203-5312
Fax: +49-761-203-5318
E-mail: szabo@pharmakol.uni-freiburg.de
Curriculum vitae
List of publications

Dr. Bela Szabo - Curriculum vitae
Name:	Szabo, Bela; MD, professor
Born:	1957 in Budapest, Hungary
Residence:	D-79104 Freiburg i. Br., Germany
Citizenship:	Until 1994 Hungarian; since 1995 German
Schools and University
1963-1971	Elementary school in Budapest
1971-1975	Secondary school at the church order "Scolae Piae" in Budapest
1975-1977	Ambulance officer at the Hungarian Ambulance Service
1977-1983	Study of medicine at the Semmelweis Medical University in Budapest
1979-1984	Participation in the research and teaching activity of the Physiological Department of the Semmelweis University
1983	Completion of the medical studies with the mark "summa cum laude". Physician´s licence for Hungary ("Approbation")
Scientific development
1983-1984	Junior scientist in the Medical Research Institute of the Hungarian Academy of Sciences
1984-1985	Guest scientist in the Department of Pharmacology of the Albert-Ludwig University in Freiburg
1986-1989	Junior scientist in the Department of Pharmacology of the Albert-Ludwig University in Freiburg
1987	MD thesis completion in the Department of Pharmacology of the Albert-Ludwig University in Freiburg; mark: "magna cum laude"
1989-1999	Postdoctoral fellow in the Department of Pharmacology of the Albert-Ludwig University in Freiburg; training as a specialist in Pharmacology and Toxicology
Since 1995	Physician´s licence for Germany ("Approbation")
1995	Specialist´s certification for Pharmacology and Toxicology ("Facharzt")
1995	PhD ("Habilitation") for Pharmacology and Toxicology
1999-2009	Reader ("Hochschuldozent; C2") in the Department of Pharmacology of the Albert-Ludwig University in Freiburg
2002	Professor ("außerplanmäßiger Professor")
Memberships in scientific organizations
Since 1983	Member of the Hungarian Physiological Society
Since 1990	Member of the German Society for Experimental and Clinical Pharmacology and Toxicology
Since 1996	Member of the Working Group for Neuropharmacology and -Toxicology (within the German Society for Experimental and Clinical Pharmacology and Toxicology)
Since 1998	Member of the International Cannabinoid Research Society
Since 1999	Advisory editor at Naunyn-Schmiedeberg´s Archives of Pharmacology
Since 2009	Member of the Review Editorial Board at Frontiers in Systems Neuroscience

Dr. rer. nat. Ilka Freiman, postdoctoral fellow

Flora Kovacs, PhD student (recipient of a DAAD scholarship)

Mario Lederer, PhD student

Sophia Linder, medical PhD student

Tim Knop, medical PhD student

Holger Schwarz, medical PhD student

Marco Spehl, medical PhD student

Previous member: Dr. rer. nat. Michal Urbanski

Present address:
Department of Biological Sciences
Room HN834 Hunter College of City University
New York, NY 10065, USA
Phone: 00-1-212- 772-5295
E-mail: MUrbanski@GENECTR.HUNTER.CUNY.EDU or murbans@hunter.cuny.edu

Previous member: Dr. rer. nat. Wolfram Bär

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Contact

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie
Albert-Ludwigs-Universität
Albertstrasse 25
D-79104 Freiburg i. Br.
Germany
Telefon: +49-761-203-5312
Fax: +49-761-203-5318
E-mail: szabo@pharmakol.uni-freiburg.de

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