Serotonin depletion impairs waiting but not stop-signal reaction time in rats: implications for theories of the role of 5-HT in behavioral inhibition.
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.
Eagle
Dawn M
DM
Department of Experimental Psychology and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. de102@cam.ac.uk
Lehmann
Olivia
O
Theobald
David E H
DE
Pena
Yolanda
Y
Zakaria
Rasheed
R
Ghosh
Rhia
R
Dalley
Jeffrey W
JW
Robbins
Trevor W
TW
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003216:Conditioning, Operant; D003913:Dextroamphetamine / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011930:Reaction Time; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage
D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine