Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main families of psychotropic drugs have been almost fortuitously discovered, from investigations carried out directly in humans. The burst of studies triggered by these discoveries and the considerably strengthened ethical guidelines for clinical trials have allowed remarkable developments in preclinical studies performed in animals, and especially in rodents. The corresponding models may be classified as follows: homologous models mimicking the aetiology of the disease against which one attempts to develop drugs; isomorphic models mimicking specific symptoms of a disease but involving different aetiological mechanisms; predictive models, which assess the effect of a drug on behavioural or other functional signs/symptoms unconnected to the psychiatric disease but involving the same type of biological targets as those affected by the disease; and theoretical or explanatory models that aim to elucidate the mechanism of action of agents producing psychotropic effects. Among the latter, the following can be cited: the knock out of genes coding for a specific biological target; the neutralisation of a specific ARNm by antisense oligodeoxynucleotides, which also aims to prevent the synthesis of a specific biological target; use of controlled reproduction to achieve a concentration of genes, the association of which leads to the development of a disease. Each one of these approaches has been illustrated by an example developed within the Rouen Neuropsychopharmacology Unit: the psychobehavioural spectrum of mice with invalidation of the gene coding for adenosine A2A receptors; the abolition of either nociceptin ORL1 receptors or neurotensin NTR2 receptors in order to characterise their functions; the concentration, by controlled breeding in mice, of a phenotype corresponding to that of depression. These developments illustrate several recent developments in neuropsychopharmacology with the aim of emphasising the vitality of this discipline.
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PMID:[The importance of in vivo pharmacology in fundamental research on psychotropic drugs and their biological targets]. 1519 68

Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such "programmed" effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood.
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PMID:Maternal separation enhances conditioned fear and decreases the mRNA levels of the neurotensin receptor 1 gene with hypermethylation of this gene in the rat amygdala. 2483 Dec 31