Behavioural signs of depression and apoptosis in the limbic system following myocardial infarction: effects of sertraline.
Depression is diagnosed in 15-30% of patients following myocardial infarction (MI) and this may also be observed in the rat. We measured the effects of the antidepressant sertraline on behavioural and biochemical events following MI in a rat model. Following surgery, MI rats and sham controls were treated with sertraline (10 mg/kg, i.p.) or saline. Subgroups of rats were tested for behavioural depression 14 days after surgery. Apoptosis was estimated in other rats by measuring caspase-3 activity and TUNEL positive cells (3 days after surgery) in limbic structures (amygdale, hippocampus, hypothalamus, frontal and prefrontal cortices). Bax/Bcl-2 ratio was measured 14 days after surgery. Behavioural signs of depression (decreased sucrose intake and forced swimming time) were found in saline-treated MI rats but not in sertraline-treated rats. Compared with controls, caspase-3 activity and TUNEL positive cells were significantly increased in most limbic structures of MI rats. High prefrontal Bax/Bcl-2 ratio in MI rats correlated with low forced swimming time. Apoptosis was not found in sertraline-treated MI rats. These results establish the bases of a rat model of depression following MI and show for the first time that a selective serotonin reuptake inhibitor prevents both behavioural and biochemical markers in this model.
Centre de recherche, Hôpital Sacré-Coeur de Montréal, Montréal, Canada.
B P
BP
Wann
T M
TM
Bah
S
S
Kaloustian
M
M
Boucher
A M
AM
Dufort
N
N
Le Marec
R
R
Godbout
G
G
Rousseau
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation; D003863:Depression / Q000209:etiology* / Q000517:prevention & control*; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020280:Sertraline / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000928:Antidepressive Agents; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D020280:Sertraline