Antidepressant-Like Behavioral Effects in 5-Hydroxytryptamine1A and 5-Hydroxytryptamine1B Receptor Mutant Mice
The development of serotonin receptor knockout mice has provided an opportunity to study antidepressant drug effects in animals with targeted genetic deletion of receptors involved in antidepressant responses. In the current study, the effects of two types of antidepressant drugs, the selective sero...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 298; no. 3; p. 1101 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Pharmacology and Experimental Therapeutics
01.09.2001
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Online Access | Get full text |
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Summary: | The development of serotonin receptor knockout mice has provided an opportunity to study antidepressant drug effects in animals
with targeted genetic deletion of receptors involved in antidepressant responses. In the current study, the effects of two
types of antidepressant drugs, the selective serotonin reuptake inhibitors fluoxetine and paroxetine and the selective norepinephrine
reuptake inhibitor desipramine, were examined in 5-hydroxytryptamine (5-HT) 1A and 5-HT 1B receptor mutant mice using the tail suspension test (TST). Under baseline conditions, the immobility of 5-HT 1A receptor mutant mice, but not 5-HT 1B receptor mutant mice, was significantly lower than that of wild-type mice. The decreased baseline immobility in 5-HT 1A receptor mutant mice was reversed by pretreatment with α-methyl- para -tyrosine, but not by para -chlorophenylalanine, suggesting mediation by enhanced catecholamine function. In wild-type mice, fluoxetine (10.0â20.0 mg/kg
i.p.) and desipramine (5.0â20.0 mg/kg i.p.) both significantly decreased immobility in the TST. In 5-HT 1A receptor mutant mice, desipramine (20.0 mg/kg i.p.) significantly decreased immobility, whereas fluoxetine (20.0 mg/kg i.p.)
and paroxetine (20.0 mg/kg i.p.) had no effect. The immobility of 5-HT 1B receptor mutant mice was decreased similarly by desipramine (5.0â20.0 mg/kg i.p.). However, the effect of low doses of fluoxetine
were significantly augmented in the 5-HT 1B receptor mutant mice (2.5â20.0 mg/kg i.p.) compared with wild-type mice. Administration of selective 5-HT receptor antagonists
in wild-type mice partially reproduced the phenotypes of the mutant mice. These results suggest that 5-HT 1A and 5-HT 1B receptors have different roles in the modulation of the response to antidepressant drugs in the TST. |
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ISSN: | 0022-3565 1521-0103 |