The effect of antidepressant drugs on the HPA axis activity, glucocorticoid receptor level and FKBP51 concentration in prenatally stressed rats.
Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity is thought to be an important factor in pathogenesis of depression. In animals, stress or glucocorticoids given in prenatal period lead to long-lasting behavioral and neuroendocrine changes similar to those observed in depressed patients. However, molecular basis for HPA disturbances in animals exposed to prenatal stress - a model of depression - have been only partially recognized. Therefore, in the present study we investigated the effect of prenatal stress on behavioral changes, blood corticosterone level, concentrations of glucocorticoid receptor (GR) and its cochaperone, FKBP51, in the hippocampus and frontal cortex in adult rats. It has been found that prenatally stressed rats display high level of immobility in the Porsolt test and anxiety-like behavior. The HPA axis hyperactivity in theses animals was evidenced by corticosterone hypersecretion at the end of the light phase and 1h following acute stress. Western blot study revealed that GR level was significantly elevated in the hippocampus but not in the frontal cortex of prenatally stressed rats, whereas concentration of FKBP51 was decreased only in the former brain structure. Chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine have diminished both behavioral and biochemical alterations observed in this animal model of depression. These data indicate that the increase in hippocampal GR level and low concentration of FKBP51 in the frontal cortex may be responsible for enhanced glucocorticoid action in depression.
Szymańska
Magdalena
M
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smetna 12, Poland.
Budziszewska
Bogusława
B
Jaworska-Feil
Lucylla
L
Basta-Kaim
Agnieszka
A
Kubera
Marta
M
Leśkiewicz
Monika
M
Regulska
Magdalena
M
Lasoń
Władysław
W
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D005625:Frontal Lobe / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D008027:Light; D008297:Male; D009994:Osmolar Concentration; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000378:metabolism*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism; D013550:Swimming / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000032:analysis / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
D000928:Antidepressive Agents; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5