1. ¹Department of Experimental Psychology and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
2. ²Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

Correspondence: Dr DM Eagle, Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Site, Cambridge CB2 3EB, UK. Tel: +44 1223 333550; Fax: +44 1223 333564; E-mail: de102@cam.ac.uk

Received 10 July 2008; Revised 29 September 2008; Accepted 6 October 2008; Published online 12 November 2008.

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 dose-dependent, 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.