Translational research in psychiatric diseases
- Principle investigator:
- Francesc Artigas
- Contact details:
Past and current research by the “Systems Neuropharmacology” team, is focused on the pathophysiology of severe psychiatric disorders (major depression, schizophrenia) and the mechanism of action of psychotropic drugs. We conducted pioneering work to identify serotonin (5-HT) autoreceptors as a main cause of he delayed and limited clinical antidepressant action. Subsequently, we used the 5-HT1A receptor/ß-adrenoceptor antagonist pindolol to hasten the clinical action of SSRIs.
More recently, we showed that the selective knockdown of 5-HT1A autoreceptors in vivo with small interference RNA (siRNA) is sufficient to evoke robust antidepressant-like effects in mice. Likewise, we have examined network mechanisms in antipsychotic action, by studying their effects in prefrontal cortex and how they normalize neurotransmitter alterations in schizophrenia. We developed a new functional model of antipsychotic drug action, based on the reversal by these drugs of cortical alterations induced by hallucinogens (NMDA-R antagonists and 5-HT2A-R agonists).
We mainly use in vivo techniques (intracerebral microdialysis, single unit and local field potential recordings, behavioral paradigms, etc.). In recent years, we have incorporated the use of small interference RNA (siRNA) techniques as well as new histological and molecular methods (e.g., track tracing techniques combined with in situ hybridization, gene expression, etc.).
Selected publications from last 5 yr:
- Bortolozzi et al., (2012) Mol Psychiatry PMID:21808255
- Lladó-Pelfort et al (2012) Cereb Cortex PMID:21893679
- Adell et al. (2012) Schizophrenia Bull PMID: 21965469
- Kargieman et al., (2012) Neuropsychopharmacol 37:723-33
- Santana et al. (2012) Biol Psychiatry 69:918-27
- Santana et al., (2009) Cereb Cortex 19:849-860
- Vázquez-Borsetti et al., (2009) Cereb Cortex 19:1678-86
- Celada et al. (2008) Biol Psychiatry 64:392-400
- Kargieman et al (2007) Proc Natl Acad Sci USA 104:14843-14848
Other relevant papers:
- Diaz-Mataix et al., (2005) J Neurosci 25:10831-10843
- Artigas et al., (2001)Trends Pharmacol Sci 22:224-228
- Martin-Ruiz et al., (2001) J Neurosci 21:9856-9866
- Celada et al., (2001) J Neurosci 21:9917-9929
- Pérez et al., (1997) Lancet 349:1594-1597
- Artigas et al. (1996) Trends Neurosci 19:378-383
- Artigas et al., (1994) Arch Gen Psychiatry 51:248-251
major depression, schizophrenia, neurotransmission, antidepressant drugs, antipsychotic drugs, brain circuits
Research is supported by Spanish and EU grants (IMI-NEWMEDS). One of the current main challenges is to develop an animal model of depression based on functional alterations of selected cortical areas, mimicking neuroimage findings in depressed patients. Research is likely to involve some or all of the above techniques. Previous experience on in vivo work is required. Experience on some of the above techniques is also desirable.
Candidates must also have a PhD in Neuroscience or related discipline. They must have relevant publications in high impact factor journals. The selected candidate will work in close interaction with the PI and the rest of the team to achieve the main research goal.
Duties and responsabilities include the design, setting up and execution of experiments in consultation with the PI, data analysis, report and paper writing s well as other research activities at the team and the Institute. Based on the previous experience of the team, a successful outcome of the research program will result in an average publication of one paper per year in top journals (first decile) in the fields of Neuroscience, Psychiatry or Pharmacology.
Team strategic objective in IDIBAPS
The objectives of the research program are fully coincident with the strategic objectives of the team “Experimental Neuropharmacology and Neuropathology” of IDIBAPS Area 4 (Clinical and Experimental Neuroscience), as defined in /research/113/neuropharmacology-and-experimental-neuropathology.
In this regard, past and present research objectives of the team are fully translational, in an attempt to improve psychiatric treatments from a better knowledge of brain function in normal and altered sates.(Read eligibility criteria)