Orbitofrontal cortex and amygdalar over-activity is associated with an inability to use the value of expected outcomes to guide behaviour in serotonin transporter knockout rats

Serotonin transporter knockout rats show improved strategy set-shifting and reduced latent inhibition

“…However, previous experiments performed with 5-HTT 2/2 rats did not provide any evidence for the notion that 5-HTT 2/2 rats exhibit a consolidation/retention deficit (e.g., Nonkes et al 2010Nonkes et al , 2011. Hence, it is unlikely that this contributed to the observed improved set-shift performance.…”

“…In analogy with the 5-HTTLPR findings, 5-HTT knockout (5-HTT 2/2 ) rats and mice show-next to increased anxiety-and depression-like behaviors (Kalueff et al 2010)-improved performance in a reversal learning task (Brigman et al 2010;Nonkes et al 2011) and functional changes in prefrontal areas subserving reversal learning (orbitofrontal cortex; OFC) and extradimensional set-shifting (medial prefrontal cortex; mPFC) (Ragozzino 2007;Wellman et al 2007;Nonkes et al 2010;Keeler and Robbins 2011;Pang et al 2011). Therefore we hypothesized that 5-HTT 2/2 rats also show improved extradimensional set-shifting.…”

“…Specifically, the orbitofrontal cortex (OFC) is implicated in reversal learning (McAlonan and Brown 2003;Ghods-Sharifi et al 2008), the medial prefrontal cortex (mPFC) in extradimensional (strategy) set-shifting (Ragozzino et al 1999;Floresco et al 2008), and latent inhibition paradigms (George et al 2010). As anatomical and task-related functional changes in these regions have been reported in 5-HTT 2/2 rodents (Wellman et al 2007;Nonkes et al 2010;Pang et al 2011), the observed genotype differences in reversal learning (Nonkes et al 2011) and the EDSS and latent inhibition paradigms (present study) might relate to altered OFC and mPFC function. In line, we specifically observed a genotype effect on mPFC-dependent perseverative errors, but not regressive or never-reinforced errors, which are thought to be more striatum-dependent (Floresco et al 2009).…”

Behavioural therapy based on distraction alleviates impaired fear extinction in male serotonin transporter knockout rats

“…[20][21][22] For example, 5-HTT -/-rodents show morphologic changes in prefrontal cortical and amygdala pyramidal neurons, 8 alterations in neocortical cell density, 23 and differential c-Fos (immediate early gene, marker for neur onal activity) immunoreactivity in the amygdala and prefrontal cortex in reaction to extinction of conditioned behaviour. 24 Alterations in these corticolimbic circuits, such as a functional uncoupling between the prefrontal cortex and amygdala 25,26 and amygdala hyperreactivity in reaction to fearful stimuli (i.e., angry faces) 27 have also been described in human s-allele carriers. Intriguingly, a recent study revealed that patients with PTSD had abnormally reduced amygdala 5-HTT expression, as measured using positron emission tomog raphy.…”

Reward processing by the dorsal raphe nucleus: 5-HT and beyond

“…For example, knocking out SERT reduces mouse reward-seeking behaviors (Sanders et al 2007) but improves reversal learning (Brigman et al 2010). SERT knockout rats are unable to change behaviors based on expected reward values in a Pavlovian reinforcer devaluation paradigm (Nonkes et al 2010), and respond excessively to the conditioned stimuli in an operant conditioning task (Nonkes and Homberg 2013). Knocking out Tph2 results in impulsivity, hyper-aggression, and abnormal sociosexual behaviors (Savelieva et al 2008;Liu et al 2011;Angoa-Perez et al 2012;Kane et al 2012;Zhang et al 2013;Gutknecht et al 2015).…”