Modulation of Frontostriatal Interaction Aligns with Reduced Primary Reward Processing under Serotonergic Drugs

Abstract

Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of the in vivo mechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.

Superiority illusion arises from resting-state brain networks modulated by dopamine

“…Indeed, a recent pharamacologic study found that the antidepressant efficacy of SSRIs modulated the FC between ventral striatum and anteroventral prefrontal cortex, which is associated with the reward system (36). Networks related to depressive behavior may coexist in different loops between striatum and prefrontal areas, and thus the superiority illusion in particular might be best viewed as the products of larger-scale interactions of different loops and different molecular systems.…”

Effects of depression on reward-based decision making and variability of action in probabilistic learning

“…In our study, depressed undergraduates who were not taking antidepressant medication completed a probabilistic selection task. Recent functional neuroimaging studies have shown that antidepressant medication affects areas of the brain reward system such as the striatum (Abler, Gron, Hartmann, Metzger, & Walter, 2012;McCabe & Mishor, 2011;Ossewaarde et al, 2011). In one study, antidepressant medication led to increased activation of the brain reward system of previously unmedicated MDD patients, such that there were no significant differences between medicated MDD patients and healthy controls (Stoy et al, 2012).…”

(S)-citalopram influences amygdala modulation in healthy subjects: a randomized placebo-controlled double-blind fMRI study using dynamic causal modeling

“…Though the amygdala has primarily been linked to an array of processes related to negative emotions, such as conditioning and memory of fear (Kim et al, 2013), fMRI studies have challenged this notion by showing amygdala and OFC reactivity in response to appetitive stimuli, possibly reflecting these regions' role in reward and motivation related behavioral processes (Gottfried et al, 2003). In fact, serotonin also seems to play a central role in these processes, as previously highlighted by Kranz et al (Kranz et al, 2010) and empirically supported by recent studies on SSRI-related sexual dysfunction (Abler et al, 2011) and biased reward processing (Abler et al, 2012). Investigations into anatomical and functional networks integrating the OFC and the amygdala describe both direct, from limbic and sensory regions, and indirect information flow to the amygdala via the OFC.…”