Zach V Redding1, Pooja Chawla2, Karen E Sabol3. 1. Department of Psychology, The University of Mississippi, PO Box 1848, University, MS, 38677, USA. 2. Virginia Commonwealth University Health System, Richmond, VA, USA. 3. Department of Psychology, The University of Mississippi, PO Box 1848, University, MS, 38677, USA. ksabol@olemiss.edu.
Abstract
RATIONALE: Norepinephrine (NE) is involved in the control of sustained attention. Studies of sustained attention in humans include measures of reaction time (RT) and RT variability (RTV). The present study tested the role of NE using components of the RT distribution in rats in a manner thought to be similar to human studies of RTV. OBJECTIVES: This study tested the effects of increased synaptic NE (atomoxetine (ATX)) and α-2 receptor binding (guanfacine) on attentional lapses in rats. METHODS: Male Sprague-Dawley rats (n = 20) were trained and tested in a two-choice RT task (2CRTT). Atomoxetine dose (saline, 0.1, 0.5, 1.0 mg/kg, i.p.), guanfacine dose (saline, 0.01, 0.1, 0.3 mg/kg, i.p.), and distractors were manipulated in three experiments. RT was divided into initiation time (IT) and movement time (MT). Analyses of distribution mode (peak) and deviation from the mode (skew) were then performed. RESULTS: ATX and guanfacine had no effect on IT mode, reduced IT devmode, and increased MT mode. When distractors were introduced, ATX again improved devmode, but a lack of interaction between ATX and distractor indicated that ATX did not prevent distractor-induced impairments. CONCLUSIONS: IT devmode is a measure of distribution skew thought to reflect lapses of attention. The effects of ATX on IT devmode suggest that increased synaptic NE reduces attentional lapses. These findings are consistent with human reports of reduced RTV after ATX administration. The same pattern of results with guanfacine suggests that the effects of increased NE are due in part to binding at α-2 noradrenergic receptors.
RATIONALE: Norepinephrine (NE) is involved in the control of sustained attention. Studies of sustained attention in humans include measures of reaction time (RT) and RT variability (RTV). The present study tested the role of NE using components of the RT distribution in rats in a manner thought to be similar to human studies of RTV. OBJECTIVES: This study tested the effects of increased synaptic NE (atomoxetine (ATX)) and α-2 receptor binding (guanfacine) on attentional lapses in rats. METHODS: Male Sprague-Dawley rats (n = 20) were trained and tested in a two-choice RT task (2CRTT). Atomoxetine dose (saline, 0.1, 0.5, 1.0 mg/kg, i.p.), guanfacine dose (saline, 0.01, 0.1, 0.3 mg/kg, i.p.), and distractors were manipulated in three experiments. RT was divided into initiation time (IT) and movement time (MT). Analyses of distribution mode (peak) and deviation from the mode (skew) were then performed. RESULTS:ATX and guanfacine had no effect on IT mode, reduced IT devmode, and increased MT mode. When distractors were introduced, ATX again improved devmode, but a lack of interaction between ATX and distractor indicated that ATX did not prevent distractor-induced impairments. CONCLUSIONS: IT devmode is a measure of distribution skew thought to reflect lapses of attention. The effects of ATX on IT devmode suggest that increased synaptic NE reduces attentional lapses. These findings are consistent with human reports of reduced RTV after ATX administration. The same pattern of results with guanfacine suggests that the effects of increased NE are due in part to binding at α-2 noradrenergic receptors.
Entities:
Keywords:
ADHD; Atomoxetine; Distractors; Distribution skew; Guanfacine; Lapses of attention; Norepinephrine; Rat; Reaction time variability; α-2 noradrenergic receptors
Authors: L Scahill; P B Chappell; Y S Kim; R T Schultz; L Katsovich; E Shepherd; A F Arnsten; D J Cohen; J F Leckman Journal: Am J Psychiatry Date: 2001-07 Impact factor: 18.112
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