TY - JOUR
T1 - Estradiol-sertraline synergy in ovariectomized rats
AU - Sell, Stacy
AU - Craft, Rebecca M.
AU - Seitz, Patricia K.
AU - Stutz, Sonja J.
AU - Cunningham, Kathryn A.
AU - Thomas, Mary L.
N1 - Funding Information:
Funding for this study was provided by a young investigator award from the National Alliance for Research on Schizophrenia and Depression (NARSAD) to S.L.S. Sertraline was generously donated by Pfizer, Inc. (Groton, CT). Neither NARSAD nor Pfizer, Inc. had any further role in study design; in the collection, analysis and interpretation of the data; nor in the writing of the report and in the decision to submit the paper for publication.
PY - 2008/9
Y1 - 2008/9
N2 - This study investigated estradiol (E2) modulation of the antidepressant effects of a selective serotonin (5-HT) reuptake inhibitor (SSRI; sertraline) and a tricyclic antidepressant (imipramine) as measured by the forced swim test (FST) followed by assessment of gene and protein expression for the 5-HT transporter (SERT) and multiple 5-HT receptors. Female Sprague-Dawley rats were ovariectomized (OVX) and two-thirds of the rats received E2 implants (OVE). 4 weeks later, implants were withdrawn in half of the OVE rats (OVW) to capture a time point when E2 levels were rapidly declining. Rats in each hormone group were treated with vehicle, sertraline (10 mg/kg) or imipramine (10 mg/kg), 24, 5 and 1 h before the FST. Immediately after the FST, midbrain, hippocampus and prefrontal cortex tissue was removed and frozen for analysis of gene expression via quantitative real-time PCR (midbrain tissue) and protein expression via Western blot (prefrontal cortex and hippocampal tissue). In the FST, sertraline decreased immobility and increased swimming in OVE rats, as well as increased swimming in OVW rats. In contrast, no sertraline effect was observed in OVX rats. Rats treated with imipramine showed increased climbing but no changes in immobility or swimming. No changes in protein expression were detected in any treatment group. However, in vehicle-treated rats, E2 increased midbrain SERT mRNA expression, with no effect on midbrain mRNA for the 5-HT receptors. In sertraline-treated rats, E2 decreased 5-HT2A receptor mRNA, and E2-withdrawal increased 5-HT1A, 5-HT2A and 5-HT2C receptor mRNA. In imipramine-treated rats, E2 (and E2-withdrawal) did not affect mRNA expression for any of the target genes. Thus, E2 synergized behaviorally and neurochemically with an SSRI but not a tricyclic antidepressant.
AB - This study investigated estradiol (E2) modulation of the antidepressant effects of a selective serotonin (5-HT) reuptake inhibitor (SSRI; sertraline) and a tricyclic antidepressant (imipramine) as measured by the forced swim test (FST) followed by assessment of gene and protein expression for the 5-HT transporter (SERT) and multiple 5-HT receptors. Female Sprague-Dawley rats were ovariectomized (OVX) and two-thirds of the rats received E2 implants (OVE). 4 weeks later, implants were withdrawn in half of the OVE rats (OVW) to capture a time point when E2 levels were rapidly declining. Rats in each hormone group were treated with vehicle, sertraline (10 mg/kg) or imipramine (10 mg/kg), 24, 5 and 1 h before the FST. Immediately after the FST, midbrain, hippocampus and prefrontal cortex tissue was removed and frozen for analysis of gene expression via quantitative real-time PCR (midbrain tissue) and protein expression via Western blot (prefrontal cortex and hippocampal tissue). In the FST, sertraline decreased immobility and increased swimming in OVE rats, as well as increased swimming in OVW rats. In contrast, no sertraline effect was observed in OVX rats. Rats treated with imipramine showed increased climbing but no changes in immobility or swimming. No changes in protein expression were detected in any treatment group. However, in vehicle-treated rats, E2 increased midbrain SERT mRNA expression, with no effect on midbrain mRNA for the 5-HT receptors. In sertraline-treated rats, E2 decreased 5-HT2A receptor mRNA, and E2-withdrawal increased 5-HT1A, 5-HT2A and 5-HT2C receptor mRNA. In imipramine-treated rats, E2 (and E2-withdrawal) did not affect mRNA expression for any of the target genes. Thus, E2 synergized behaviorally and neurochemically with an SSRI but not a tricyclic antidepressant.
KW - Antidepressant
KW - Estrogen
KW - Forced swim test
KW - Selective serotonin reuptake inhibitor
KW - Serotonin receptors
KW - Serotonin transporter
UR - http://www.scopus.com/inward/record.url?scp=49049115706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49049115706&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2008.05.006
DO - 10.1016/j.psyneuen.2008.05.006
M3 - Article
C2 - 18650020
AN - SCOPUS:49049115706
SN - 0306-4530
VL - 33
SP - 1051
EP - 1060
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 8
ER -