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Behavioural signs of depression and apoptosis in the limbic system following myocardial infarction: effects of sertraline

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada

TM Bah

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada

S Kaloustian

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada; Department of Pharmacology, Université de Montréal, Montréal, Canada

M Boucher

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada; Department of Pharmacology, Université de Montréal, Montréal, Canada

AM Dufort

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada

N Le Marec

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada; Department of Psychiatry, Université de Montréal, Montréal, Canada

R Godbout

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada; Department of Psychiatry, Université de Montréal, Montréal, Canada

G Rousseau

Centre de recherche, Hôpital Sacré-Cœur de Montréal, Montréal, Canada; Department of Pharmacology, Université de Montréal, Montréal, Canada

Abstract

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.

Key Words: anhedonia • apoptosis • behavioural despair • depression model • serotonin uptake

This version was published on June 1, 2009

Journal of Psychopharmacology, Vol. 23, No. 4, 451-459 (2009)
DOI: 10.1177/0269881108089820


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