Neurochemical Modulation of Response Inhibition and Probabilistic Learning in Humans

Serotonin does not seem to mediate performance of the Stop-signal task, as SSRIs and serotonin depletion did not affect action cancelation in humans or animals.

“Serotonin does not seem to mediate performance of the Stop-signal task, as use of selective serotonin re-uptake inhibitors (SSRIs) and serotonin depletion did not affect action cancelation in humans or in animals (Clark et al., 2005; Chamberlain et al., 2006b; Bari et al., 2009; Eagle et al., 2009; Drueke et al., 2010).”

Administration of methylphenidate and atomoxetine decreases SSRT in humans and animals, raising the possibility that noradrenalin is involved in motor response inhibition.

“Administration of methylphenidate and atomoxetine, which both target the dopamine and noradrenalin system, by inhibiting the re-uptake from the synaptic cleft, decreased SSRT in humans and in animals, raising the possibility that noradrenalin is involved in motor response inhibition as well (Chamberlain et al., 2006b; Eagle et al., 2007; Bari et al., 2009; Nandam et al., 2011).”

Studies examining acute administration of SSRIs have shown impaired probabilistic learning, impaired cognitive flexibility, but increased long-term memory recall, emotion recognition, and harm aversion for moral judgements.

“Studies examining the acute administration of SSRIs have shown impaired probabilistic learning [19, 20], and impaired cognitive flexibility [20], but increased long-term memory recall [21], emotion recognition [22], and harm aversion for moral judgements [23].”

In human studies, the noradrenergic reuptake inhibitor atomoxetine enhanced stop-signal performance but had no effect on probabilistic learning known to engage OFC mechanisms, whereas the selective serotonin reuptake inhibitor citalopram had the reverse pattern of effects.

“In human studies, the noradrenergic reuptake inhibitor atomoxetine enhanced stop-signal performance but had no effect on probabilistic learning known to engage OFC mechanisms, whereas the selective serotonin reuptake inhibitor citalopram had the reverse pattern of effects [132].”

One study showed that response inhibition improved with SSRI administration, whereas another showed no effect.

“One study showed that response inhibition improved with SSRI administration [20], whereas another showed no effect [19].”

Chamberlain et al. showed no acute effect of the SSRI citalopram on response inhibition.

“However, in line with our results, Chamberlain et al. [19] showed no acute effect of the SSRI citalopram on response inhibition.”

In humans, both normal subjects and patients with ADHD show improved PFC inhibition of behavior following atomoxetine, consistent with the animal data.

“In humans, both normal subjects (Chamberlain et al., 2006), and patients with ADHD (Chamberlain et al., 2007) show improved PFC inhibition of behavior following atomoxetine, consistent with the animal data.”

Citalopram does not correct response inhibition deficits in human or animal studies.

“However, this seems specific to fluoxetine, as citalopram, another SSRI, does not correct deficits in response inhibition in either human or animal studies (Chamberlain et al 2006, Clark et al 2005, Eagle et al 2008a, Eagle et al 2009).”