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.
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Acknowledgements
This study was supported by a Wellcome Trust Programme Grant (076274/z/04/z) awarded to TWR, BJ Everitt, BJ Sahakian, and AC Roberts and completed within the University of Cambridge Behavioral and Clinical Neuroscience Institute, supported by a joint award from the Medical Research Council and the Wellcome Trust. OL was supported by a Marie Curie Fellowship. YP was supported by a predoctoral Formaci?n Investigadora scholarship from Generalitat de Catalunya.
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TWR discloses consultancy for Cambridge Cognition, Eli Lilly Inc., Wyeth, GlaxoSmithKline, and Allon Therapeutics, receives grant/research support from Pfizer, GlaxoSmithKline, and is a major stock shareholder in CeNeS, Cambridge Cognition, Allon Therapeutics. DME, OL, DEHT, YP, RZ, RG, and JWD have no disclosures.
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Eagle, D., Lehmann, O., Theobald, D. et al. Serotonin Depletion Impairs Waiting but not Stop-Signal Reaction Time in Rats: Implications for Theories of the Role of 5-HT in Behavioral Inhibition. Neuropsychopharmacol 34, 1311–1321 (2009). https://doi.org/10.1038/npp.2008.202
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