Influence of acute or chronic administration of ovarian hormones on the effects of desipramine in the forced swim test in female rats

Abstract

Rationale Gender may influence antidepressant (AD) treatment outcome. In order to address this pre-clinically, the potential effects of ovarian hormones on AD treatment in ovariectomized female rats were investigated. Objectives In the first study, the effect of acute administration of estrogen and progesterone on the antidepressant-like effects of desipramine (DMI), a selective norepinephrine reuptake inhibitor (SNRI), was investigated in the forced swimming test (FST). In the second study, the effect of chronic administration of these hormones on the effects of chronically administered DMI was investigated. Results In the acute study, the hormones blocked the effects of DMI in the FST as demonstrated by the absence of either a reduction in immobility or an increase in climbing behavior in animals treated with DMI in combination with the hormones. Concentration-response experiments on hippocampal synaptosomes revealed no changes in the Km or Bmax for uptake of 3H-NE in hormone-treated rats. In the chronic study, the antidepressant-like effects of DMI in the FST were not blocked by chronic administration of hormones. Interestingly, the hormones affected the serum concentrations of DMI. These levels were significantly higher in animals receiving 10 or 15 mg/kg/day in hormone-treated rats as compared to those with placebo. Conclusions Acute administration of hormones blocked the effects of DMI (given three times over 24 h) in the FST. However, chronic administration of these hormones failed to block the effects of chronically administered DMI (at a dose that produces clinically relevant serum concentrations).

Sex Differences in Antidepressant Effect of Sertraline in Transgenic Mouse Models

“…However, estrogen injection was associated with a decrease of 5-HT levels and an increased 5-HT turnover rate (Pandaranandaka et al, 2006), or showed no differences in OVX female rat (Lu et al, 1998). It is worth to note that most of the estrogen-dependent changes of 5-HT-related depressive behaviors in animals were associated with estrogen administration acutely or chronically (Shah and Frazer, 2014) which might be different from endogenous estrogen in related to the serotonergic system (Pandaranandaka et al, 2009). Instead of treating animals with exogenous estrogen, studies of 5-HT metabolism in female animals at young, middle and old ages demonstrated that young female animals exhibited higher hippocampal 5-HT concentration than middle-age animals (Kiss et al, 2012), and women over 60 years of age had less platelet 5-HT content than younger age (Guicheney, 1988).…”

Sexually dimorphic responses of rats to fluoxetine in the forced swimming test are unrelated to the function of the serotonin transporter in the brain

“…Absent or paradoxical responses to fluoxetine (Li et al, ; Pic‐Taylor et al, ) or other antidepressants (Ribeiro et al, ; Thelen, Sens, Mauch, Pandit, & Pitychoutis, ) were previously observed in female rats. Sexual hormones may impact the responses of female rats to fluoxetine (Benmansour, Weaver, Barton, Adeniji, & Frazer, ; Craft, Kostick, Rogers, White, & Tsutsui, ; de Oliveira et al, ; De Vry, Maurel, Schreiber, De Beun, & Jentzsch, ; Enríquez‐Castillo et al, ; Estrada‐Camarena, López‐Rubalcava, Hernández‐Aragón, Mejía‐Mauries, & Picazo, ; Estrada‐Camarena, Rivera, Berlanga, & Fernández‐Guasti, ; Flores‐Serrano et al, ; Gomez et al, ; Li et al, ; Lifschytz, Shalom, Lerer, & Newman, ; McNamara et al, ; Mitic, Simic, Djordjevic, Radojcic, & Adzic, ; Molina‐Hernández & Téllez‐Alcántara, , ; Pic‐Taylor et al, ; Récamier‐Carballo, Estrada‐Camarena, Reyes, & Fernández‐Guasti, ; Sell et al, ; Shah & Frazer, ). Indeed, ovariectomized rats, with or without estrogen replacement, presented male‐like response to fluoxetine in the FST (Benmansour et al, ; Estrada‐Camarena et al, ; Estrada‐Camarena et al, ; Gomez et al, ; Molina‐Hernández & Téllez‐Alcántara, , ; Récamier‐Carballo et al, ; Sell et al, ; Shah & Frazer, ) while intact females continue to display no response (Pic‐Taylor et al, ) or paradoxical response (Li et al, ).…”

Adolescent chronic restraint stress (aCRS) elicits robust depressive-like behavior in freely cycling, adult female rats without increasing anxiety-like behaviors.

“…The single publication on the effect of desipramine on FST behaviors in freely cycling rats measured the behaviors of Wistar rats during daily 5-min swims for 42 consecutive days in a shallow FST chamber, and a scoring system incompatible with the standard modified method (Contreras, Martínez-Mota, & Saavedra, 1998). The literature that has differentiated between active behaviors in the FST has consistently reported significantly more climbing behaviors elicited by desipramine (Detke et al, 1997; Shah & Frazer, 2014; Slattery & Cryan, 2012). Although most of the studies reporting increased climbing used subacute dosing (three doses in 24 hours prior to testing), one used a chronic dosing regimen with a final dose given 30 min prior to testing (Detke et al, 1997), and another used a chronic dosing regimen via osmotic pump (Shah & Frazer, 2014).…”

“…Desipramine, a standard tricyclic antidepressant, was used as a positive control to evaluate the predictive validity of the aCRS model. Desipramine’s antidepressant effect is primarily attributed to blockade of the norepinephrine reuptake transporter (NET) and has been associated with increased climbing behaviors in the FST in male (Detke et al, 1997; Slattery & Cryan, 2012) and ovx rats (Shah & Frazer, 2014). Desipramine (Sigma-Aldrich, St. Louis, MO) dissolved in 0.9% NaCl (saline) was given subcutaneously (SC) at a dose of 5 mg/kg.…”

“…The most widely used measure of behavioral despair in rats is the forced swim test (FST) (Porsolt, Le Pichon, & Jalfre, 1977). Immobility in the FST is used to quantify the depressive-like behaviors of the animals modeling depression (Bourke & Neigh, 2011; Brenes Sáenz, Villagra, & Fornaguera Trías, 2006; Dalla, Pitychoutis, Kokras, & Papadopoulou-Daifoti, 2010; Hong et al, 2012; Huynh, Krigbaum, Hanna, & Conrad, 2011), and active behaviors in the FST (swimming and climbing) have been used to screen for antidepressant actions of drugs (Detke, Johnson, & Lucki, 1997; Shah & Frazer, 2014; Slattery & Cryan, 2012). Diving may also be presented, but it is a less-common active behavior, and has not been correlated with a pharmacological action.…”