Patients with attention-deficit/hyperactivity disorder (ADHD) show various cognitive impairments such as deficits in attention or working memory. Most symptoms of ADHD are thought to be associated with a dysbalance between the neurotransmitters noradrenaline and dopamine in the brain. In order to investigate the role of noradrenaline in this context we have produced a central depletion of noradrenaline in rats by administering different doses (10, 20 or 50 mg/kg body weight) of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) and assessing the behavioral consequences with a modified hole board task. The administration of DSP4 affected the working memory error, while reference memory and motor functions were not affected. The use of different doses of DSP4 to influence prefrontal functions and to understand the dysbalance of dopamine and noradrenaline in ADHD appears to be a promising approach.

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The present study investigated the effects of nutritional omega-3 polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats (SHRs), which are used as an animal model of attention-deficit/hyperactivity disorder (ADHD). For 6 weeks, two groups of randomly assigned SHRs received food either enriched with or deficient in omega-3 fatty acids (based on the American Institute of Nutrition-93 G/AIN93G). Using an open field, locomotor activity was subsequently assessed for 6 days. A marked difference in locomotor activity as assessed by the distance travelled in the open field was found between the two groups of rats. In comparison with rats fed with omega-3 fatty acid-enriched food, the animals on the omega-3 fatty acid-deficient diet showed a significantly higher locomotor activity. The present findings demonstrated that nutritional enrichment with omega-3 fatty acids was associated with reduced motor activity in an established animal model of ADHD and support the notion that omega-3 polyunsaturated fatty acids may play a role in the pathophysiology of ADHD.

The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats' performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats.

ABSTRACT:Background: Attention deficit hyperactivity disorder (ADHD) is the most frequent behavioral disorder of childhood and is characterized by hyperactivity, attention problems and impulsivity. Pharmacological and behavioral therapies have been shown to be effective. In addition, the role of dietary compounds in the etiology and possibly the treatment of ADHD has attracted increasing attention. For example, the lack of dietary essential fatty acids has been suggested to be associated with symptoms of ADHD in humans.Objective: To investigate the effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on locomotor activity in the spontaneously hypertensive rat (SHR) which has been proposed as an animal model of ADHD.Methods: Two groups of randomly assigned spontaneously hypertensive rats were fed with either n-3 PUFA-deficient or n-3 PUFA-enriched food (based on AIN93G) for six weeks and this was continued during the phase of behavioral testing. Locomotor activity was subsequently assessed using an open field test. Results:The results showed a marked difference in locomotor activity between the two groups of SHRs. In comparison with rats fed with n-3 deficient food, the animals on an n-3 enriched diet showed a statistically significant decrease in motor activity as assessed by the distance traveled. Conclusions:The present study demonstrates a marked reduction in locomotor activity following an n-3 PUFA-enriched diet in SHRs, i.e. the dietary enrichment with n-3 PUFAs reduced the motor activity in an established animal model of ADHD. Dietary n-3 PUFAs may therefore play a role in the pathophysiology of ADHD.