Deficits in fine motor skills in a genetic animal model of ADHD

Abstract

Background: In an attempt to model some behavioral aspects of Attention Deficit/Hyperactivity Disorder (ADHD), we examined whether an existing genetic animal model of ADHD is valid for investigating not only locomotor hyperactivity, but also more complex motor coordination problems displayed by the majority of children with ADHD.

Methods: We subjected young adolescent Spontaneously Hypertensive Rats (SHRs), the most commonly used genetic animal model of ADHD, to a battery of tests for motor activity, gross motor coordination, and skilled reaching. Wistar (WIS) rats were used as controls.

Results: Similar to children with ADHD, young adolescent SHRs displayed locomotor hyperactivity in a familiar, but not in a novel environment. They also had lower performance scores in a complex skilled reaching task when compared to WIS rats, especially in the most sensitive measure of skilled performance (i.e., single attempt success). In contrast, their gross motor performance on a Rota-Rod test was similar to that of WIS rats.

Conclusion: The results support the notion that the SHR strain is a useful animal model system to investigate potential molecular mechanisms underlying fine motor skill problems in children with ADHD.

Figure 1

SHRs show increased locomotor and rearing activity. Naïve SHR and WIS rats were exposed to an activity/open field box and their spontaneous motor activity was recorded for 1 h. (A) Distance traveled (meters) as a function of time during the 60 min open field test. (B) Representative tracks of movement patterns of SHR and WIS rats during the initial 10 min of testing and at the 50-60 min time interval of testing. Distance traveled and rearing activity are shown in brown and blue colors, respectively. (C) Number of rears as a function of time during the 60 min open field test. All data (A and C) are represented as mean ± S.M.E. (N = 5 animals per group). *P < 0.05, **P < 0.001 when compared to WIS rats.

Figure 2

SHRs are hyperactive and have decreased response habituation. Naïve SHR and WIS rats were exposed to an activity/open field box for 1 h on day one (see Figure 1) and were re-exposed to the same testing box for two consecutive days. (A) Average distance traveled (meters) during the initial 10 min of testing. (B) Average distance traveled (meters) during the 20-60 min interval of testing. All data are represented as mean ± S.M.E. (N = 5 animals per group). *P < 0.05, **P < 0.001 when compared to WIS rats.

Figure 3

SHRs show increased levels of rearing activity. Naïve SHR and WIS rats were exposed to an activity/open field box for 1 h on day one (see Figure 1) and were re-exposed to the same testing box for two consecutive days. (A) Average number of rears during the initial 10 min of testing. (B) Average number of rears during the 20-60 min interval of testing. All data are represented as mean ± S.M.E. (N = 5 animals per group). *P < 0.05, **P < 0.001 when compared to WIS rats.

Figure 4

Deficits in skilled reaching behavior in SHRs. Endpoint measures of reaching behavior are presented: (A) Total success in percentage, (B) Success on the first reach in percentage, and (C) Attempts. *P < 0.05 when compared to WIS rats. The results are presented as mean ± S.E.M. (N = 8 per group).

Figure 5

Similar performance of young adolescent SHR and WIS rats in the Rota-Rod test. Mean (± S.M.E.) latency to fall on indicated trials for SHR and WIS rats (N = 8 animals per group).