Serotonin Depletion Impairs Waiting but not Stop-Signal Reaction Time in Rats: Implications for Theories of the Role of 5-HT in Behavioral Inhibition

Abstract

Central serotonin (5-HT) function is thought to be a critical component of behavioral inhibition and impulse control. However, in recent clinical studies, 5-HT manipulations failed to affect stop-signal reaction time (SSRT), which is a fundamental process in behavioral inhibition. We investigated the effect of central 5-HT depletion (intracerebroventricular 5,7-dihydroxytryptamine) in rats on two aspects of behavioral inhibition, SSRT and 'waiting', using the stop-signal task. 5-HT depletion had no effects on SSRT or any other primary measure on the stop-signal task. However, within the same task, there was a deficit in 'waiting' in 5-HT-depleted rats when they were required to withhold from responding in the terminal element of the stop-signal task for an extended period. D-Amphetamine had dosedependent, but not 5-HT-dependent effects on SSRT. Conversely, the dose that tended to improve, or decrease, SSRT (0.3 mg/kg) impaired the ability to wait, again independently of 5-HT manipulation. These findings suggest that SSRT and 'waiting' are distinct measures of behavioral inhibition, and show that 5-HT is critical for some forms of behavioral inhibition but not others. This has significant implications for the treatment of conditions such as attention deficit and hyperactivity disorder, substance abuse, and affective disorders, in which inhibitory and impulse-control deficits are common.

Forebrain overexpression of CK1δ leads to down-regulation of dopamine receptors and altered locomotor activity reminiscent of ADHD

“…Recent studies have focused on mechanisms of behavioral inhibition and pinpointed the integration of a network including the orbitofrontal cortex, the dorsomedial striatum, and the subthalamic nucleus, that normally inhibits many forms of behavior, including both impulsivity and compulsivity (for a review, see ref. 29). Our behavioral data suggest that overexpression of CK1δ in the forebrain might disturb this network balance and produce some form of impulsivity.…”

Serotonin Depletion Induces ‘Waiting Impulsivity’ on the Human Four-Choice Serial Reaction Time Task: Cross-Species Translational Significance

“…Thus, TD was found to affect Go/NoGo responding to a greater extent in males with a history of alcoholism (LeMarquand et al, 1999) or in healthy volunteers where responding was suppressed by punishment (Crockett et al, 2009). By contrast, TD had no effect on stop-signal reaction-time performance in healthy subjects Cools et al, 2005) in parallel with a similar lack of effect of serotonin depletion in rats (Eagle et al, 2009).…”

Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

“…Thus, studies in rats and humans have shown that manipulating 5-HT does not affect performance on tasks of inhibition that have no clear affective component, such as the stop-signal reaction-time task Cools et al, 2005;Chamberlain et al, 2006;Bari et al, 2009;Eagle et al, 2009), the self-ordered spatial working memory task (Walker et al, 2009), and the go-nogo task (Rubia et al, 2005;Evers et al, 2006) (but see LeMarquand et al, 1999).…”