Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice.

The 5-HT(4) receptor is a new potential target for antidepressant treatment and may be implicated in the pathogenesis of depression. This study investigated differences in 5-HT(4) receptor and 5-HT transporter (5-HTT) binding by quantitative autoradiography of [(3)H]SB207145 and (S)-[N-methyl-(3)H]citalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control.

Transcriptional changes in insulin- and lipid metabolism-related genes in the hippocampus of olfactory bulbectomized mice.

Affymetrix chips were used to perform a hypothesis-free large-scale screening of transcripts in the hippocampus of olfactory bulbectomized mice, an established animal model of depression. Because only 11 transcripts were significantly changed, the statistically subsequent 25 transcripts below the significance level were additionally included in a first round of qRT-PCR evaluations. Furthermore, all 36 genes were then tested for mutual interactions or interactions with other molecules in a physiological context using PathwayArchitect software.

Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas.

The olfactory bulbectomy in rodents has been proposed as an animal model for depression. According to the neurotrophin and monoamine hypotheses of depression, the present study examined neurotrophin and monoamine (serotonin, norepinephrine, dopamine) levels in several depression-related brain regions of mice subjected to olfactory bulbectomy. As expected, bulbectomized animals revealed behavioral alterations such as locomotor hyperactivity and reduced gain of bodyweight, regarded as correlates of a depressive-like state.