Effect of desipramine on gene expression in the mouse frontal cortex - microarray study.

BACKGROUND: These studies aimed to identify the genes differentially expressed in the frontal cortex of mice treated repeatedly with either saline or desipramine (DMI). METHODS: Differences in gene expression in the mouse frontal cortex were studied using a whole-genome microarray approach. RESULTS: The analyses revealed a group of 88 transcripts (18 genes) that were differentially expressed between the mice treated with saline and those treated with DMI. These genes include Spnb2, Mef2c, Ncam1, Hsp90ab1, Kif1b, Ddx6 and Gsk3b, which were connected in the gene relationship network. CONCLUSIONS: It appears that one week of DMI administration measurably altered the expression of a small number of genes, including genes connected with neuroplasticity and cytoskeletal changes, the regulation of calcium levels in the cell or translation processes.

Potential role of G protein-coupled receptor (GPCR) heterodimerization in neuropsychiatric disorders: a focus on depression.

G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins in the human genome and are the target of approximately half of all therapeutic drugs. For many years, GPCRs were thought to exist and function as monomeric units. However, during the past two decades, substantial biochemical, structural and functional evidence have indicated that GPCRs can associate and form heteromers that exhibit functional properties distinct from the corresponding monomers. The understanding of the unique pharmacological and functional properties of such heteromers is a major challenge for neuroscience, particularly given the abundant evidence suggesting that GPCR heteromers may play a crucial role in neuropsychiatric disorders. Herein, we present current data on the role of GPCR heterodimerization in neuropsychiatric disorders, with a focus on its potential implications in depression. The presented examples of pairs of receptors, with their specific pharmacological and functional properties, are likely to lead to novel effective strategies in antidepressant drug development. The currently available techniques for studying GPCR heterodimerization, both in vitro as well as in situ in native tissue, are also described.

Involvement of prolactin and somatostatin in depression and the mechanism of action of antidepressant drugs.

Neuropeptides have been implicated in the physiology and pathophysiology of stress responses and therefore may play an important role in the pathogenesis of affective disorders such as Major Depression Disorder (MDD). The data presented in this mini-review demonstrate the role of prolactin (PRL) and somatostatin (STT) in the pathology and pharmacotherapy of MDD, focusing particularly on the response to antidepressant treatment, and compare the available data with the results obtained in our laboratory using the well-validated chronic mild stress (CMS) animal model of MDD. Despite the availability of many pharmacological therapies for depression, ca. 35% patients remain treatment resistant. This clinical situation is also true for rats subjected to CMS; some animals do not respond to antidepressant therapy and are considered treatment resistant. The most interesting results presented in this mini-review concern the changes in PRL and SST receptors in the brains of rats subjected to the full CMS procedure and IMI treatment and demonstrate the role of these receptors in the mechanisms of antidepressant action. The possible interaction between SST and PRL, the involvement of the D2 dopamine receptor, and their direct protein-protein interactions are also discussed, with the conclusion that these two neurohormones play an important role in the mechanism of resilience after stress as well as in the mechanism of action of antidepressant drugs.

Antidepressant drugs promote the heterodimerization of the dopamine D2 and somatostatin Sst5 receptors--fluorescence in vitro studies.

BACKGROUND: The interaction between the dopaminergic and somatostatinergic systems and their role in mood regulation have been well-documented. Therefore, we decided to investigate the effect of antidepressant drugs on the heterodimerization of the dopamine D2 and somatostatin Sst5 receptors. METHODS: The human receptor proteins were tagged with fluorescent proteins, expressed in the HEK 293 cells and incubated with antidepressant drugs: desipramine and citalopram. To determine the FRET efficiency, the fluorescence resonance energy transfer (FRET) and photobleaching confocal microscopy techniques were used. RESULTS: We found that the efficiency of FRET is markedly increased in cells coexpressing the somatostatin Sst5 and dopamine D2 receptors after 48 h of incubation with desipramine and citalopram. CONCLUSIONS: In the present study we provide physical evidence, based on FRET analysis, that antidepressants increase Sst5 and D2 receptors heterodimerization. The effect is specific because desipramine in the incubation medium uncouples other pairs of receptors, such as the dopamine D1-D2 receptors.