TY - JOUR

T1 - Differential effects of ADHD medications on impulsive action in the mouse 5-choice serial reaction time task

AU - Fitzpatrick, Ciarán M

AU - Andreasen, Jesper T

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Aberrant impulsivity is found in a number of psychiatric disorders including attention deficit hyperactivity disorder (ADHD). The 5-choice serial reaction time task (5-CSRTT) is a paradigm commonly used to assess impulsive control. We recently developed a protocol to habituate mice to a variable intertrial interval (vITI) schedule before assessing pharmacological effects on "waiting" impulsivity. This study aimed to develop on that initial investigation by testing the effects of three conventional ADHD medications. Consistent premature response rates were achieved in male C57BL/6 J mice in the first week out of 15 vITI (5-, 10- or 15-s) days (four training days followed by one drug treatment day per week for three weeks) before each drug study commenced. The effects of atomoxetine (1, 3 mg/kg), methylphenidate (1, 2 mg/kg) and guanfacine (0.03, 0.1 mg/kg) were investigated using a Latin-square design. High- and low-impulsive subgroups were determined based on initial training day data before the drug studies initiated. Both 1 and 3 mg/kg atomoxetine reduced premature responding at the 10- (P < 0.001, P < 0.05) and 15-s (P < 0.001) lengths. 2 mg/kg methylphenidate increased impulsive action at the longest 15-s ITI (P < 0.05). Guanfacine exerted no effects on premature responding rates at any dose or ITI. Impulsive subgrouping did not reveal any specific drug by subgroup effects. This study indicates that these current ADHD medications have differential effects on impulsive action. In summary, this protocol is a useful preclinical model for testing potential treatments for disorders with dysfunctional impulsive control.

AB - Aberrant impulsivity is found in a number of psychiatric disorders including attention deficit hyperactivity disorder (ADHD). The 5-choice serial reaction time task (5-CSRTT) is a paradigm commonly used to assess impulsive control. We recently developed a protocol to habituate mice to a variable intertrial interval (vITI) schedule before assessing pharmacological effects on "waiting" impulsivity. This study aimed to develop on that initial investigation by testing the effects of three conventional ADHD medications. Consistent premature response rates were achieved in male C57BL/6 J mice in the first week out of 15 vITI (5-, 10- or 15-s) days (four training days followed by one drug treatment day per week for three weeks) before each drug study commenced. The effects of atomoxetine (1, 3 mg/kg), methylphenidate (1, 2 mg/kg) and guanfacine (0.03, 0.1 mg/kg) were investigated using a Latin-square design. High- and low-impulsive subgroups were determined based on initial training day data before the drug studies initiated. Both 1 and 3 mg/kg atomoxetine reduced premature responding at the 10- (P < 0.001, P < 0.05) and 15-s (P < 0.001) lengths. 2 mg/kg methylphenidate increased impulsive action at the longest 15-s ITI (P < 0.05). Guanfacine exerted no effects on premature responding rates at any dose or ITI. Impulsive subgrouping did not reveal any specific drug by subgroup effects. This study indicates that these current ADHD medications have differential effects on impulsive action. In summary, this protocol is a useful preclinical model for testing potential treatments for disorders with dysfunctional impulsive control.

KW - Adrenergic Uptake Inhibitors/pharmacology

KW - Animals

KW - Atomoxetine Hydrochloride/pharmacology

KW - Attention/drug effects

KW - Attention Deficit Disorder with Hyperactivity/drug therapy

KW - Central Nervous System Stimulants/pharmacology

KW - Choice Behavior/drug effects

KW - Impulsive Behavior/drug effects

KW - Male

KW - Methylphenidate/pharmacology

KW - Mice

KW - Mice, Inbred C57BL

KW - Reaction Time/drug effects

U2 - 10.1016/j.ejphar.2019.01.038

DO - 10.1016/j.ejphar.2019.01.038

M3 - Journal article

C2 - 30690006

VL - 847

SP - 123

EP - 129

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -