Individual and combined effects of physical exercise and methylphenidate on orienting behavior and social interaction in spontaneously hypertensive rats

Abstract

This study determined the duration of exercise and amount of methylphenidate that is needed to affect attentional function and social behavior in spontaneously hypertensive rats (SHR), a commonly used animal model of Attention-Deficit/Hyperactivity Disorder (ADHD). Attention was assessed by measuring the orienting response to repeated presentations of a nonreinforced visual cue. Social behavior was examined by allowing rats to freely explore a large arena containing an unfamiliar conspecific rat. Consistent with their hyper-responsive phenotype, nonexercising SHRs exhibited a high level of orienting behavior and little habituation, as well as hyper-social behavior compared with normo-active rats. Exercise or methylphenidate decreased orienting behavior and social behavior in a dose-dependent fashion. In addition, we found an additive effect of combining doses of exercise and methylphenidate that alone were ineffective in altering behavior. These data indicate that physical exercise and methylphenidate can reduce hyper-responsiveness to irrelevant stimuli and reduce hyper-social behavior in SHR. Moreover, subthreshold doses of methylphenidate can be used in combination with moderate amounts of exercise to reduce distractibility, supporting the notion that exercise may be useful as an adjunctive or replacement therapy in ADHD.

Figure 1

Unconditioned orienting (rearing behavior) observed during repeated presentations of a non-reinforced visual stimulus. The number of breaks in the photobeams used to detect rearing behavior is shown on the y-axis. Blocks of trials (first 4, middle 4, and last 4 trials) are shown on the x-axis. Rearing behavior did not habituate in the saline-treated SHRs. MPH treated SHRs did show habituation of the orienting response across blocks of trials, with the exception of the 0.015 mg/kg dose. Data are means ± the SE.

Figure 2

The average number of social interactions made by each group (panel A). The number of social interactions reflects the number of contacts made by an experimental rat with holes in the cylinder containing the target rat during a 10-min session. A 0.125 mg/kg dose of MPH reduced the number of social interactions initiated, as compared to saline-treated SHRs. No other MPH doses significantly reduced social interaction behavior. There were no differences in locomotor activity during the session (panel B). Locomotor activity data reflect the number of times rats in each group crossed either of two lines that separated the arena into thirds. Data are means ± SE.

Figure 3

Unconditioned orienting (rearing behavior) observed during repeated presentations of a non-reinforced visual stimulus. The number of breaks in the photobeams used to detect rearing behavior is shown on the y-axis. Blocks of trials (first 4, middle 4, and last 4 trials) are shown on the x-axis. There was a significant difference between non-exercising SHRs and all other groups, with the exception of the 2 day exercise group. Data are means ± the SE.

Figure 4

The average number of social interactions made by each group in (panel A). The number of social interactions reflects the number of contacts made by an experimental rat with holes in the cylinder containing the target rat during a 10-min session. 21 days of exercise reduced the number of social interactions initiated, as compared to non-exercising SHRs. 5 and 10 days of exercise did not alter social interaction behavior. Locomotor activity data reflect the number of times rats in each group crossed a line that separated the arena into thirds (panel B). There were no differences in locomotor activity between controls and exercising SHRs. Data are means ± SE.

Figure 5

Unconditioned orienting (rearing behavior) observed during repeated presentations of a non-reinforced visual stimulus. The number of breaks in the photobeams used to detect rearing behavior is shown on the y-axis. Blocks of trials (first 4, middle 4, and last 4 trials) are shown on the x-axis. Rearing behavior did not habituate in the non-exercising, saline-treated SHRs. SHRs that received 2 days of exercise and a 0.015625 mg/kg MPH did show habituation of the orienting response across blocks of trials. Data are means ± the SE.

Figure 6

The average number of social interactions made by each group in (panel A). The number of social interactions reflects the number of contacts made by an experimental rat with holes in the cylinder containing the target rat during a 10-min session. A 0.0625 mg/kg dose of MPH combined with 10 days of exercise did not reduce the number of social interactions initiated, as compared to saline-treated non-exercising SHRs. There were no differences in locomotor activity during the session (panel B). Locomotor activity data reflect the number of times rats in each group crossed either of two lines that separated the arena into thirds. Data are means ± SE.