Effects of escitalopram on the regulation of brain-derived neurotrophic factor and nerve growth factor protein levels in a rat model of chronic stress.
Escitalopram (ES-CIT) is a widely used, highly specific antidepressant. Until now there has been very little evidence on how this drug under pathological conditions affects an important feature within the pathophysiology of stress-related disorders such as depression: the endogenous neurotrophins. By using a well-characterized rat model in which chronic stress induces depressive-like behavior, the levels of neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined in representative brain regions and serum using a highly sensitive improved fluorometric two-site ELISA system. There was a significant increase of BDNF in the left and right cortices after stress treatment (twofold increase) that was reversed by application of ES-CIT. An ES-CIT-dependent NGF reduction in stressed rats was detectable in the right cortex only (P = 0.027). The left hippocampus revealed significantly higher amounts of BDNF (2.5-fold increase) protein than the right hippocampus. These interhemispheric differences were unrelated to stress or ES-CIT treatment in all animals. BDNF and NGF of the frontal cortex, cerebellum, and serum did not change between the study groups. There was a negative correlation between body weight and serum BDNF, independent of stress or ES-CIT treatment. In conclusion, BDNF and NGF show substantial changes in this rodent model of chronic social stress, which is susceptible to antidepressant treatment with ES-CIT and therefore may constitute a neurobiological correlate for the disease.
Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
Olaf
O
Schulte-Herbrüggen
Eberhard
E
Fuchs
Nashat
N
Abumaria
Annerose
A
Ziegler
Heidi
H
Danker-Hopfe
Christoph
C
Hiemke
Rainer
R
Hellweg
D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism*; D002908:Chronic Disease / Q000188:drug therapy; D015283:Citalopram / Q000494:pharmacology*; D004291:Dominance-Subordination; D004327:Drinking Behavior / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D007839:Functional Laterality; D016014:Linear Models; D008297:Male; D020932:Nerve Growth Factor / Q000097:blood / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*
D018687:Antidepressive Agents, Second-Generation; D019208:Brain-Derived Neurotrophic Factor; D015283:Citalopram; D020932:Nerve Growth Factor