An influence of delayed reinforcement on the effectiveness of psychostimulants to enhance indices of attention under a five-choice serial reaction time procedure in male rats

Abstract

The five-choice serial reaction time (5-CSRT) procedure has been considered a translational tool for assessments of the psychopharmacology of attention in preclinical research. Because greater sensitivity to delayed reinforcement may promote the development of attention-deficit/hyperactivity disorder (ADHD) symptoms, effects of reinforcer delay and psychostimulants on performances under a 5-CSRT procedure were determined. Male rats were trained to respond under a 5-CSRT procedure with different delay-of-reinforcement conditions (0, 2, 4, 8, 16 s), and effects of d-amphetamine, methylphenidate, and morphine (as a negative control) were assessed at 0- and 16-s delays. Under nondrug conditions, as the delay increased both response latency and the number of trials in which a response did not occur (omissions) increased, and the percent correct on trials when responses were emitted decreased. Only modest increases in the percent correct were found with psychostimulants during the 0-s delay condition; however, more substantial enhancements were found with a 16-s delay. Consistent effects of both psychostimulants at either delay on omissions and response latency were not observed. Morphine increased omissions and response latency at both delays and decreased the percent correct (16-s delay). Generally, responses during the intertrial interval were not systematically affected under any condition. The current results demonstrate that measures of attention in a 5-CSRT procedure are sensitive to changes in the delay to reinforcer delivery. More important, psychostimulants significantly enhanced a measure of attention only when reinforcers were delayed, which may be reflective of the psychopharmacological mechanisms involved with clinical treatment of ADHD symptoms.

Figure 1.

Effects of reinforcer delay (0–16 s) with (open triangles) and without (filled triangles) an adjusted intertrial interval (ITI) on performances under the five-choice serial reaction time (5-CSRT) procedure. Top left panel: percentage of correct responses; Top right panel: trial omissions; Bottom left panel: response latency; Bottom right panel: ITI responses. Each data point represents an average (±SEM) effect determined in six subjects. An asterisk indicates effects significantly different from 0-s delay values.

Figure 2.

Effects of methylphenidate (1.0–10.0 mg/kg) at a 0-s delay (open circle) and at a 16-s delay (filled circle) on performances under the five-choice serial reaction time (5-CSRT procedure). Top left panel: percent of correct responses; Top right panel: trial omissions; Bottom left panel: response latency; Bottom right panel: ITI responses. Each data point represents an average (±SEM) effect determined in six subjects. An asterisk indicates effects significantly different from vehicle-control values.

Figure 3.

Effects of d-amphetamine (0.1–1.7 mg/kg) at a 0-s delay (open circle) and at a 16-s delay (filled circle) on performances under the five-choice serial reaction time (5-CSRT) procedure. Top left panel: percent of correct responses; Top right panel: trial omissions; Bottom left panel: response latency; Bottom right panel: ITI responses. Each data point represents an average (±SEM) effect determined in six subjects. An asterisk indicates effects significantly different from vehicle-control values.

Figure 4.

Effects of morphine (1.0–10.0 mg/kg) at a 0-s delay (open circle) and at a 16-s delay (filled circle) on performances under the five-choice serial reaction time (5-CSRT) procedure. Top left panel: percent of correct responses; Top right panel: trial omissions; Bottom left panel: response latency; Bottom right panel: ITI responses. Each data point represents an average (±SEM) effect determined in six subjects. An asterisk indicates effects significantly different from vehicle-control values.