Insensitivity of NMRI mice to selective serotonin reuptake inhibitors in the tail suspension test can be reversed by co-treatment with 5-hydroxytryptophan.
Psychopharmacology (Berl)
; 199(2): 137-50, 2008 Aug.
Article
em En
| MEDLINE
| ID: mdl-18496675
ABSTRACT
RATIONALE Exploring differences between mouse strains in drug effects in models of antidepressant-like activity may provide clues to the neurobiology of antidepressant responses. OBJECTIVES:
The objective of this study was to explore whether insensitivity to selective serotonin reuptake inhibitors (SSRIs) in NMRI mice in the tail suspension test can be related to 5-hydroxytryptamine (5-HT) function. MATERIALS ANDMETHODS:
We compared NMRI and C57Bl/6 mice, a SSRI-sensitive strain, in the tail suspension test following citalopram, paroxetine, or fluoxetine and determined 5-HT transporter (5-HTT) densities, 5-HT tissue and extracellular levels, 5-HT synthesis, tryptophan hydroxylase 2 (TPH2) genotypes and hypothermia induced by the 5-HT(1A) agonist 8-OH-DPAT. In NMRI mice, we tested if co-treatment with 5-HTP would increase 5-HT levels and confer SSRI sensitivity in the tail suspension test.RESULTS:
C57Bl/6, but not NMRI, mice responded to SSRIs in the tail suspension test. 5-HTT densities in the frontal cortex and hippocampus were similar between the strains. NMRI mice had lower tissue 5-HT levels in these regions and decreased extracellular 5-HT in the frontal cortex at baseline and following citalopram. C57Bl/6 mice were more sensitive to 8-OH-DPAT-induced hypothermia. Both strains had the 1473C TPH2 genotype and similar 5-HT synthesis. In NMRI mice, 5-HTP co-treatment restored the tail suspension and extracellular 5-HT responses to SSRIs to levels equivalent to those seen in C57Bl/6 mice.CONCLUSION:
Low 5-HT function in NMRI mice may account for their insensitivity to SSRIs in the tail suspension test. As the tail suspension test is a predictor of clinical efficacy, the current data suggest that 5-HTP adjunct treatment may benefit SSRI treatment refractory patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
5-Hidroxitriptofano
/
Inibidores Seletivos de Recaptação de Serotonina
/
Elevação dos Membros Posteriores
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article