Since the mid of the 1960ies, striking similarities between the psychosis seen in subjects taking high doses of amphetamines and the symptoms of patients with paranoid schizophrenia have been noted and placed in the context of increased catecholaminergic neurotransmission as a fundamental cause underlying major symptoms of the disease. Subsequent studies emphasized the contribution of central dopaminergic mechanisms for at least several psychotic symptoms of schizophrenia. The most compelling pharmacological data to support the developing ”dopamine hypothesis of schizophrenia” originated from the clear relationship between antipsychotic drug efficacy and affinity for D2 - like dopamine receptors strongly indicating D2-antagonism as major if not exclusive mechanism of antipsychotic drug action. Accordingly, in this review we focus on the neuropharmacology of the dopaminergic system in our brain with special emphasis on the dopaminergic synapse.
References
-
1
Abi-Dargham A, Laruelle M.
Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies.
European Psychiatry.
2005;
20
15-27
-
2
Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles L S, Weiss R, Cooper T B, Mann J J, Van Heertum R L, Gorman J M, Laruelle M.
Increased baseline occupancy of D-2 receptors by dopamine in schizophrenia.
Proceedings of the National Academy of Sciences of the United States of America.
2000;
97
8104-8109
-
3
Bonci A, Hopf F W.
The dopamine D2 receptor: New surprises from an old friend.
Neuron.
2005;
47
335-338
-
4
Bristow L J, Kramer M S, Kulagowski J, Patel S, Ragan C I, Seabrook G R.
Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist.
Trends Pharmacol Sci..
1997;
18
186-188
-
5
Capuano B, Crosby I T, Lloyd E J.
Schizophrenia: genesis, receptorology and current therapeutics.
Curr.Med.Chem.
2002;
9
521-548
-
6
Chang W H, Jaw S S, Tsay L.
Chronic Haloperidol Treatment with Low-Doses May Enhance the Increase of Homovanillic-Acid in Rat-Brain.
European Journal of Pharmacology.
1989;
162
151-156
-
7
De Camilli P, Macconi D, Spada A.
Dopamine inhibits adenylate cyclase in human prolactin-secreting pituitary adenomas.
Nature.
1979;
278
252-254
-
8
Dresel S, Mager T, Rossmuller B, Meisenzahl E, Hahn K, Moller H J, Tatsch K.
In vivo effects of olanzapine on striatal dopamine D-2/D-3 receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study.
European Journal of Nuclear Medicine.
1999;
26
862-868
-
9
Farde L, Nordstrom A L, Karlsson P, Halldin C, Sedvall G.
Positron Emission Tomography Studies on Dopamine-Receptors in Schizophrenia.
Clinical Neuropharmacology.
1995;
18
S121-129
-
10
Farde L, Nordstrom A L, Wiesel F A, Pauli S, Halldin C, Sedvall G.
Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects.
Arch Gen Psychiatry.
1992;
49
538-544
-
11
Goldman-Rakic P S, Castner S A, Svensson T H, Siever L J, Williams G V.
Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction.
Psychopharmacology (Berl).
2004;
174
3-16
-
12
Grace A A, Bunney B S, Moore H, Todd C L.
Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs.
Trends in Neurosciences.
1997;
20
31-37
-
13
Gurevich E V, Bordelon Y, Shapiro R M, Arnold S E, Gur R E, Joyce J N.
Mesolimbic dopamine D-3 receptors and use of antipsychotics in patients with schizophrenia - A postmortem study.
Archives of General Psychiatry.
1997;
54
225-232
-
14 Huff R M. Signaling pathways modulated by dopamine receptors. 1997: 167-192
-
15
Joyce J N, Milian M J.
Dopamine D-3 receptor antagonists as therapeutic agents.
Drug Discovery Today.
2005;
10
917-925
-
16
Kapur S, Mamo D.
Half a century of antipsychotics and still a central role for dopamine D2 receptors.
Prog Neuropsychopharmacol Biol Psychiatry.
2003;
27
1081-1090
-
17
Miyamoto S, Duncan G E, Marx C E, Lieberman J A.
Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs.
Mol.Psychiatry.
2005;
10
79-104
-
18
Moller H J.
Antipsychotic and antidepressive effects of second generation antipsychotics - Two different pharmacological mechanisms?.
European Archives of Psychiatry and Clinical Neuroscience.
2005;
255
190-201
-
19
Neve K A, Seamans J K, Trantham-Davidson H.
Dopamine receptor signaling.
Journal of Receptors and Signal Transduction.
2004;
24
165-205
-
20
Nordstrom A L, Farde L, Eriksson L, Halldin C.
No Elevated D-2 Dopamine-Receptors in Neuroleptic-Naive Schizophrenic-Patients Revealed by Positron Emission Tomography and [C-11] N-Methylspiperone.
Psychiatry Research-Neuroimaging.
1995;
61
67-83
-
21
Nordstrom A L, Farde L, Wiesel F A, Forslund K, Pauli S, Halldin C, Uppfeldt G.
Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients.
Biol.Psychiatry.
1993;
33
227-235
-
22
Okubo Y, Suhara T, Sudo Y, Toru M.
Possible role of dopamine D1 receptors in schizophrenia.
Molecular Psychiatry.
1997;
2
291-292
-
23
Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M, Tateno Y, Toru M.
Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET.
Nature.
1997;
385
634-636
-
24
Seeman P.
Dopamine Receptor Sequences - Therapeutic Levels of Neuroleptics Occupy D2-Receptors, Clozapine Occupies D4.
Neuropsychopharmacology.
1992;
7
261-284
-
25 Seeman P and Kapur S. Olanzapine Binding to Dopamine Receptors in Vitro and in Vivo. In Tran, PV et al., editors. Olanzapine (Zyprexa®): A novel antipsychotic. Philadelphia: Lippincott Williams & Wilkings;. 2000.: p. 3-24
-
26
Seeman P, Kapur S.
Schizophrenia: More dopamine, more D-2 receptors.
Proceedings of the National Academy of Sciences of the United States of America.
2000;
97
7673-7675
-
27
Seeman P, Lee T, Chauwong M, Wong K.
Antipsychotic Drug Doses and Neuroleptic-Dopamine Receptors.
Nature.
1976;
261
717-719
-
28
Seeman P, Weinshenker D, Quirion R, Srivastava I AK, Bhardwaj S K, Grandy D K, Premont R T, Sotnikova T D, Boksa P, El Ghundi M, O'Dowd B F, George S R, Perreault M L, Mannisto P T, Robinson S, Palmiter R D, Tallerico T.
Dopamine supersensitivity correlates with D2(High) states, implying many paths to psychosis.
Proceedings of the National Academy of Sciences of the United States of America.
2005;
102
3513-3518
-
29
Stevens J R.
Anatomy of Schizophrenia.
Archives of General Psychiatry.
1973;
29
177-189
-
30
Strange P G.
Antipsychotic drugs: Importance of dopamine receptors for mechanisms of therapeutic actions and side effects.
Pharmacological Reviews.
2001;
53
119-133
-
31
Tauscher J, Kufferle B, Asenbaum S, Tauscher-Wisniewski S, Kasper S.
Striatal dopamine-2 receptor occupancy as measured with [I-123]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol.
Psychopharmacology.
2002;
162
42-49
-
32
Truffinet P, Tamminga C A, Fabre L F, Meltzer H Y, Riviere M E, Papillon-Downey C.
Placebo-controlled study of the D4/5-HT2A antagonist fananserin in the treatment of schizophrenia.
Am. J.Psychiatry.
1999;
156
419-425
-
33
Wadenberg M LG, Jones C, Kapur S, Soliman A, Vaccarino F, Wilson A.
Quantitative relationship between in vivo dopamine D2 receptor occupancy and catalepsy in rats.
International Journal of Psychology.
2000;
35
421
-
34
Wong D F, Young D, Wilson P D, Meltzer C C, Gjedde A.
Quantification of neuroreceptors in the living human brain. D-2-like dopamine receptors: Theory, validation, and changes during normal aging.
Journal of Cerebral Blood Flow and Metabolism.
1997;
17
316-330
Prof. Dr. W. E. Müller
Department of Pharmacology
Biocenter
Goethe University
Marie-Curie-Str. 9
D-60439 Frankfurt
Germany
Telefon: +49 69 79829373
Fax: +49 69 79829374
eMail: PharmacolNat@em.uni-frankfurt.de
