Differential effects of fluoxetine and venlafaxine on memory recognition: Possible mechanisms of action

Fluoxetine Exposure during Adolescence Alters Responses to Aversive Stimuli in Adulthood

“…Separate groups of adolescent mice were treated with VEH or FLX (10 mg/kg, twice daily) 4 h apart for 15 consecutive days [postnatal day 35 (P35) to P49]. The age at the start and duration of the experimental manipulation in both mice and rats (P35-P49) was selected because it roughly approximates mid-adolescence in humans (Andersen, 2003;Abreu-Villaça et al, 2010), a developmental stage in which the onset of MDD is most often reported (Burke et al, 1990;Paus et al, 2008). The drug regimen (20 mg/kg/d) was selected because it yields significant effects on behavior and gene expression in rodents (Englander et al, 2005;Iñiguez et al, 2010a;LaPlant et al, 2010;Surget et al, 2011).…”

“…The construction of the vectors (HSV-GFP, HSV-wtERK2, and HSV-dnERK2) has been thoroughly described (Robinson et al, 1996;Neve et al, 1997), and the ERK2 viruses have been previously validated in vivo and in vitro (Krishnan et al, 2007;Iñiguez et al, 2010c). All behavioral experiments were commenced 3 d after viral surgery, a time at which maximal transgene expression is observed (Carlezon et al, 1998;Barrot et al, 2002). Expression of the HSV-encoded transgenes was limited to an area of ϳ1 mm 3 around the injection site (see Fig.…”

“…Major depressive disorder (MDD) affects up to 8% of the juvenile population (Kapornai and Vetró , 2008), resulting in negative functional consequences that extend into adulthood (Birmaher et al, 2007). Prozac [fluoxetine (FLX)], a selective serotonin reuptake inhibitor, is a therapeutic agent approved by the Food and Drug Administration to treat pediatric MDD (Hammerness et al, 2006).…”

“…This has led to a significant increase in the prescription rate of FLX in this population (Zito et al, 2006), even though the majority of testing regarding its effectiveness and safety has been conducted in adults (Coyle et al, 2003;Olivier et al, 2011). This is remarkable given the pivotal role that the serotonin system plays in the regulation of brain development (Blakemore and Choudhury, 2006;Azmitia, 2007), that pharmacodynamic differences between developing and adult organisms are consistently reported (Iñiguez et al, 2008a;Correll et al, 2011;Neville et al, 2011), and that early-life pharmacological intervention often results in life-long neurobehavioral alterations (Bolaños et al, 2003b;Halladay et al, 2009;Oberlander et al, 2009).…”

“…Nevertheless, the antidepressant mechanisms of FLX have been linked to adaptations in postreceptor signaling since chronic, not acute, administration is required for its therapeutic effects Racagni and Popoli, 2008). For example, within the ventral teg-mental area (VTA), a brain region implicated in mood regulation (Nestler and Carlezon, 2006;Chaudhury et al, 2013), brainderived neurotrophic factor (BDNF) and its downstream signaling effectors are compromised in preclinical models of stress , as well as in postmortem VTA samples from MDD patients . Conversely, chronic administration of FLX normalizes these alterations within the VTA Cao et al, 2010).…”