5-HT(1A) RECEPTOR LIGANDS IN ANIMAL-MODELS OF ANXIETY, IMPULSIVITY AND DEPRESSION - MULTIPLE MECHANISMS OF ACTION

被引:143
作者
SCHREIBER, R
DEVRY, J
机构
[1] Institute for Neurobiology, Department of Psychopharmacology, Cologne, Troponwerke
关键词
ANIMAL MODELS; ANXIETY; DEPRESSION; 5-HT; 5-HT(1A) RECEPTORS; 5-HT(2) RECEPTORS; IMPULSIVITY;
D O I
10.1016/0278-5846(93)90034-P
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
1. Preclinical and clinical studies suggest that 5-HT1A receptor agonists are a new class of mixed axiolytics/antidepressants with, possibly, impulsivity reducing properties. 2. The anxiolytic effects of 5-HT1A receptor agonists result predominantly from an interaction with presynaptic 5-HT1A receptors (resulting in a decrease of serotonergic transmission), whereas the antidepressive and, possibly, the impulse control enhancing effects, result predominantly from an interaction with postsynaptic 5-HT1A receptors. 3. These proposed mechanism(s) of action fit well with the generally held view that anxiety is the result of a hypersensitive 5-HT system; whereas impulsivity and depression is the result of a hyposensitive 5-HT system. 4. However, it appears very likely that activation of pre- and postsynaptic 5-HT1A receptors is additionally involved in the antidepressive and impulse control enhancing effects, on the one hand, and in the anxiolytic effects of these compounds, on the other hand. 5. These latter, seemingly paradoxical, findings can be explained by assuming that (1) the presynaptic mechanism reflects an anxiolytic component in the animal models of impulsivity and depression, (2) antagonism of postsynaptic 5-HT1A receptors by these compounds contributes to their anxiolytic effects, (3) postsynaptic 5-HT1A and 5-HT2 receptors have functionally opposing effects or, alternatively, that (4) downregulation of postsynaptic 5-HT2 receptors contributes to the therapeutic effects of these compounds.
引用
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页码:87 / 104
页数:18
相关论文
共 59 条
[1]  
ARANGO V, 1991, SOC NEUR ABSTR, V17
[2]   INCREASED SEROTONIN2 (5-HT2) RECEPTOR-BINDING AS MEASURED BY H-3 LYSERGIC ACID DIETHYLAMIDE (H3-LSD) IN THE BLOOD-PLATELETS OF DEPRESSED-PATIENTS [J].
ARORA, RC ;
MELTZER, HY .
LIFE SCIENCES, 1989, 44 (11) :725-734
[3]   INCREASED NUMBER OF 5HT2 RECEPTORS IN THE LEARNED HELPLESSNESS RAT [J].
BARONE, P ;
ATGER, F ;
MARTIN, P ;
PUECH, A ;
FILLION, G .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 183 (05) :1900-1901
[4]   ANTICONFLICT AND DISCRIMINATIVE STIMULUS EFFECTS OF THE 5-HT1A COMPOUNDS WY-47,846 AND WY-48,723 AND THE MIXED 5-HT1A AGONIST 5-HT2 ANTAGONIST WY-50,324 IN PIGEONS [J].
BARRETT, JE ;
ZHANG, L .
DRUG DEVELOPMENT RESEARCH, 1991, 24 (02) :179-188
[5]  
BENJAMIN D, 1990, SOC NEUR ABSTR, V16
[6]   SMOKING-ASSOCIATED CHANGES IN THE SEROTONERGIC SYSTEMS OF DISCRETE REGIONS OF HUMAN BRAIN [J].
BENWELL, MEM ;
BALFOUR, DJK ;
ANDERSON, JM .
PSYCHOPHARMACOLOGY, 1990, 102 (01) :68-72
[7]  
BERENDSEN HHG, 1991, THESIS U GRONINGEN N
[8]  
BROWN SL, 1991, CLIN EXP PSYCH MONOG, V4
[9]   8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN, A SELECTIVE SEROTONIN1A RECEPTOR AGONIST, REDUCES THE IMMOBILITY OF RATS IN THE FORCED SWIMMING TEST BY ACTING ON THE NUCLEUS RAPHE DORSALIS [J].
CERVO, L ;
GRIGNASCHI, G ;
SAMANIN, R .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 158 (1-2) :53-59
[10]   BRAIN 5-HT2 RECEPTOR-BINDING SITES IN DEPRESSED SUICIDE VICTIMS [J].
CHEETHAM, SC ;
CROMPTON, MR ;
KATONA, CLE ;
HORTON, RW .
BRAIN RESEARCH, 1988, 443 (1-2) :272-280