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Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptor mutant mice.
J Pharmacol Exp Ther. 2001 Sep; 298(3):1101-7.JP

Abstract

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 alpha-methyl-para-tyrosine, but not by para-chlorophenylalanine, suggesting mediation by enhanced catecholamine function. In wild-type mice, fluoxetine (10.0--20.0 mg/kg i.p.) and desipramine (5.0--20.0 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 (5.0--20.0 mg/kg i.p.). However, the effect of low doses of fluoxetine were significantly augmented in the 5-HT(1B) receptor mutant mice (2.5--20.0 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.

Authors+Show Affiliations

Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6140, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11504807

Citation

Mayorga, A J., et al. "Antidepressant-like Behavioral Effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) Receptor Mutant Mice." The Journal of Pharmacology and Experimental Therapeutics, vol. 298, no. 3, 2001, pp. 1101-7.
Mayorga AJ, Dalvi A, Page ME, et al. Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptor mutant mice. J Pharmacol Exp Ther. 2001;298(3):1101-7.
Mayorga, A. J., Dalvi, A., Page, M. E., Zimov-Levinson, S., Hen, R., & Lucki, I. (2001). Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptor mutant mice. The Journal of Pharmacology and Experimental Therapeutics, 298(3), 1101-7.
Mayorga AJ, et al. Antidepressant-like Behavioral Effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) Receptor Mutant Mice. J Pharmacol Exp Ther. 2001;298(3):1101-7. PubMed PMID: 11504807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptor mutant mice. AU - Mayorga,A J, AU - Dalvi,A, AU - Page,M E, AU - Zimov-Levinson,S, AU - Hen,R, AU - Lucki,I, PY - 2001/8/16/pubmed PY - 2001/9/14/medline PY - 2001/8/16/entrez SP - 1101 EP - 7 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 298 IS - 3 N2 - 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 alpha-methyl-para-tyrosine, but not by para-chlorophenylalanine, suggesting mediation by enhanced catecholamine function. In wild-type mice, fluoxetine (10.0--20.0 mg/kg i.p.) and desipramine (5.0--20.0 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 (5.0--20.0 mg/kg i.p.). However, the effect of low doses of fluoxetine were significantly augmented in the 5-HT(1B) receptor mutant mice (2.5--20.0 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/11504807/Antidepressant_like_behavioral_effects_in_5_hydroxytryptamine_1A__and_5_hydroxytryptamine_1B__receptor_mutant_mice_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11504807 DB - PRIME DP - Unbound Medicine ER -