TY - JOUR
T1 - Response-inhibition capacity in spontaneously hypertensive and Wistar rats
T2 - Acquisition of fixed minimum interval performance and responsiveness to D-amphetamine
AU - Rojas-Leguizamón, Maryed
AU - Baroja, José L.
AU - Sanabria, Federico
AU - Orduña, Vladimir
N1 - Funding Information:
This research was supported by grants IN306415 and IN306818 from PAPIIT (Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica) and 281548 from CONACyT (Consejo Nacional de Ciencia y Tecnología). Funding was also provided by UNAM (Universidad Nacional Autónoma de México), DGAPA (Dirección General de Asuntos del Personal Académico) POSTDOC grant to Maryed Rojas; a research stay supported by DGAPA PEID (Programa de Estancia de Investigación) and a sabbatical leave from Arizona State University to Federico Sanabria; CONACyT (Grant # 265683) funded a sabbatical leave for Vladimir Orduña. The authors thank Jimena Arroyo, Ithandeui Jaimes, Sebastián Lucero, Adriana Rincón, and Elisa Thierry, for assistance in data collection, Fernando Salinas for technical assistance, Cesar Casasola and Alejandra Aguayo for help in drug preparation and manipulation, Claudia V. Rivera for her generous donation of the SHR subjects, and Ryan Brackney and Carter Daniels for their advice in the early stages of data analysis.
Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Reduced response-inhibition capacity is a defining feature of attention-deficit hyperactivity disorder. The fixed minimum interval (FMI) schedule has been systematically validated to assess such capacity in rats. On each FMI trial, the first lever press initiates an inter-response time (IRT); a potentially consummatory response terminates the IRT; only IRTs longer than a target interval result in access to food. Despite task validity, steady-state FMI performance in the most common animal model of attention-deficit hyperactivity disorder, the spontaneously hypertensive rat (SHR), is similar to normotensive control performance, even though SHR performs at lower levels, especially during acquisition, in similar response-withholding tasks. To determine whether such limitations of the model are specific to stable-state performance, this experiment compared FMI 6-s performance in SHR and Wistar rats during acquisition and in steady state, and assessed the effect of acute D-amphetamine (AMP) administration (0.1, 0.5, and 1.0 mg/kg) on steady-state performance. Median latencies to first lever press were consistently shorter in SHR than in Wistar rats; IRTs were shorter for SHR than for Wistar rats during acquisition, but substantially less so during asymptotic performance. AMP dose-dependently reduced latencies, shortened IRTs, and, at the highest dose, increased the proportion of IRTs under schedule control. These results suggest that, relative to Wistar rats, SHR have a reduced capacity to learn to withhold a reinforced response; once the FMI is acquired, high doses of D-AMP disrupt withholding performance in both strains, but they also enhance the responsiveness of both strains to reinforcement contingencies.
AB - Reduced response-inhibition capacity is a defining feature of attention-deficit hyperactivity disorder. The fixed minimum interval (FMI) schedule has been systematically validated to assess such capacity in rats. On each FMI trial, the first lever press initiates an inter-response time (IRT); a potentially consummatory response terminates the IRT; only IRTs longer than a target interval result in access to food. Despite task validity, steady-state FMI performance in the most common animal model of attention-deficit hyperactivity disorder, the spontaneously hypertensive rat (SHR), is similar to normotensive control performance, even though SHR performs at lower levels, especially during acquisition, in similar response-withholding tasks. To determine whether such limitations of the model are specific to stable-state performance, this experiment compared FMI 6-s performance in SHR and Wistar rats during acquisition and in steady state, and assessed the effect of acute D-amphetamine (AMP) administration (0.1, 0.5, and 1.0 mg/kg) on steady-state performance. Median latencies to first lever press were consistently shorter in SHR than in Wistar rats; IRTs were shorter for SHR than for Wistar rats during acquisition, but substantially less so during asymptotic performance. AMP dose-dependently reduced latencies, shortened IRTs, and, at the highest dose, increased the proportion of IRTs under schedule control. These results suggest that, relative to Wistar rats, SHR have a reduced capacity to learn to withhold a reinforced response; once the FMI is acquired, high doses of D-AMP disrupt withholding performance in both strains, but they also enhance the responsiveness of both strains to reinforcement contingencies.
KW - Animal models
KW - attention-deficit hyperactivity disorder
KW - d-amphetamine
KW - impulsivity
KW - response inhibition
KW - spontaneous hypertensive rat
UR - http://www.scopus.com/inward/record.url?scp=85056352874&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056352874&partnerID=8YFLogxK
U2 - 10.1097/FBP.0000000000000411
DO - 10.1097/FBP.0000000000000411
M3 - Article
C2 - 29877871
AN - SCOPUS:85056352874
SN - 0955-8810
VL - 29
SP - 668
EP - 675
JO - Behavioural pharmacology
JF - Behavioural pharmacology
IS - 8
ER -