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The prevalence of obesity in children and adolescents has increased rapidly over the past 30 years, as has the incidence of attention deficit hyperactivity disorder (ADHD). In 2012, it was found that overweight children have a twofold higher chance of developing ADHD than their normal weight counterparts. Previous work has documented learning and memory impairments linked to consumption of an energy-dense diet in rats, but the relationship between diet and ADHD-like behaviors has yet to be explored using animal models. Therefore, the purpose of this study was to explore the role of diet in the etiology of attention and hyperactivity disorders using a rat model of diet-induced obesity. Male Sprague-Dawley rats were fed either a control diet or a Western-style diet (WSD) for ten weeks, and specific physiological and behavioral effects were examined. Tail blood samples were collected to measure fasting blood glucose and insulin levels in order to assess insulin insensitivity. Rats also performed several behavioral tasks, including the open field task, novel object recognition test, and attentional set-shifting task. Rats exposed to a WSD had significantly higher fasting insulin levels than controls, but both groups had similar glucose levels. The quantitative insulin sensitivity check index (QUICKI) indicated the development of insulin resistance in WSD rats. Performance in the open field test indicated that WSD induced pronounced hyperactivity and impulsivity. Further, control diet animals were able to discriminate between old and novel objects, but the WSD animals were significantly impaired in object recognition. However, regardless of dietary condition, rats were able to perform the attentional set-shifting paradigm. While WSD impaired episodic memory and induced hyperactivity, attentional set-shifting capabilities are unaffected. With the increasing prevalence of both obesity and ADHD, understanding the potential links between the two conditions is of clinical relevance., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In a previous study, we reported a rat model of early-life limbic seizures which resulted in a loss of GABA(B) receptor inhibition in the hippocampus. Since gating of auditory evoked potentials in the hippocampus (auditory gating) requires GABA(B) receptors and spatial behaviors depend on the hippocampus, we hypothesize that rats with early-life limbic seizures manifest deficits of auditory gating and spatial behaviors. Seizure rats were given a single injection of GABA(B) receptor antagonist CGP56999A (1-1.2 mg/kg i.p.) on postnatal day (PND) 15, which induced multiple limbic seizures in 8h; control rats were given saline injection. When tested at 3-9 weeks after seizure/control treatment, seizure as compared to control rats showed no difference in finding a hidden platform in the water maze, but were deficient in learning and maintaining consecutive criterion performance in the 8-arm radial arm maze. Auditory gating, as measured by paired-click (conditioning followed by test click) average auditory evoked potentials in the hippocampus, revealed a significant difference between seizure rats and controls. Seizure as compared to control rats showed an increased ratio of the test to conditioning click response as adolescents (50 days old) or adults (70 days old). Heterosynaptic electric paired-pulse depression of hippocampal population excitatory postsynaptic potential in freely moving rats, a measure of hippocampal GABA(B)-receptor mediated inhibition, was decreased in seizure as compared to control rats. Seizure as compared to control rats showed increased locomotor activity in a novel open field for the first 10 min, and decreased activity at 15-60 min. However, auditory prepulse inhibition, a measure of sensorimotor gating, revealed no difference between seizure and control rats. In conclusion, early-life limbic seizures induced a long-lasting deficit in auditory gating, likely caused by GABA(B) receptor-mediated inhibition loss in the hippocampus. Auditory gating loss is a symptom of schizophrenia, and thus GABA(B) receptor inhibition loss in the hippocampus provides a mechanism linking early-life seizures to a psychiatric symptom., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Investigators tested the hypothesis that administration of the NMDA antagonist ketamine would result in differential effects on activity levels in rats depending upon the age and the sex of the animal. Twenty-two-, 35-, and 50-day-old rats were given doses of ketamine (0.0 or 10.0 mg/kg) and tested for open-field activity and frequencies of reverse locomotion, rearing, turning, and head weaving. Results indicated that ketamine produced hyperactivity in both males and females at 22 days of age but only in females at 35 days of age. There was no effect of ketamine on locomotor activity in 50-day-old rats, regardless of sex. Effects of ketamine on turning, reverse locomotion, and head weaving were similar with administration, in general, causing increments in these behaviors in both sexes at 22 days and in females at all ages tested. Ketamine resulted in reductions in rearing in both sexes regardless of age.

We have studied the effects of inescapable electric foot shocks (ISs) on rats by using a subsequent avoidance/escape task performed in a shuttle box as an animal model of post-traumatic stress disorder (PTSD). In this study, the behavioral differences and the effects of chronic stress exposure prior to IS were examined among male rats of the Wistar, Fischer 344, and Lewis strains. In concordance with our previous report on the Wistar rats, we observed the characteristic features of PTSD in all three rat strains tested, that is, the hyperactive and hypoactive bidirectional behavioral changes that are associated with hypervigilant and hyperarousal behavior, and the numbing and avoidant behavior, respectively. The induction of hypoactive behaviors after IS was most exaggerated in the Fischer and Lewis strains. Although the count of hyperactive behaviors was maximal in the Fischer strain both at basal levels without IS and after IS, the increase in the rate of hyperactive behaviors by IS was the most prominent in the Lewis strain. In addition, preloaded chronic variable stress (CVS) enhanced the degree of hyperactive behavioral changes in the Wistar strain. Thus, we consider that the present study further validates the use of shuttle box paradigm as an animal model of PTSD by demonstrating the vulnerability due to genetic background and environmental preloaded stress.

Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa. In ABA, scheduled feeding in combination with voluntary wheel running leads to hyperactivity, reduced food intake, severe body weight loss and hypothermia. In this study it was investigated whether hyperactivity in ABA could be reduced by introducing a warm plate (which was voluntary accessible and did not influence ambient temperature) into a part of the cage. In ad libitum fed rats, the presence of the warm plate did not influence body temperature, running wheel activity (RWA), body weight or food intake. During ABA, however, rats preferred the warm plate and hypothermia was prevented, while hyperactivity and body weight loss were significantly reduced when compared to ABA rats without a plate. Correlation analysis revealed a significant association between basal body temperature and RWA during the light phase in ABA rats. However, there was no evidence that initiation of light phase RWA was a result of hypothermia. These data suggest that ABA rats prefer to prevent hypothermia passively by choosing a warm plate rather than actively regulating body temperature by hyperactivity.

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel--a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)-it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.

We have previously shown that excitation of certain neurons in the ventromedial nucleus of the hypothalamus (VMH) of rats induces hyperrunning activity. The present study investigated the involvement of these VMH neurons in inducing excessive running under the activity-stress paradigm. The VMH of 6-week-old male rats was bilaterally lesioned by administration of kainic acid. Control animals received saline in the VMH. They were housed in running-wheel activity cages with free access to food for 6 days of the recovering period, and then fed 1 h each day for 6 days. Control animals exhibited marked increases in both running activity and its light/dark ratio, and developed stomach ulcers. In contrast, animals with bilateral VMH lesions showed a significantly attenuated increase in running activity and no change in light/dark ratio. VMH lesions also suppressed stomach ulceration. These results suggest that VMH neurons play a crucial role in inducing excessive running and stomach ulceration during exposure to the activity-stress paradigm.

In this work, we report a new analysis system to quantify the behavioral disorders observed in the model of the rat submitted to high pressure and monitored by piezoelectric sensor. The major advance consists in a spectral 3D representation of LMA and tremor, which provides a better selectivity than previous systems. This behavioral processing indicated that tremor is characterized by a 7-14 Hz frequency band and LMA by a 20-35 Hz frequency band. The association of this system to the microdialysis technique to simultaneously evaluate the striatal DA level confirms that pressure-induced striatal DA increase is in great part linked to the LMA, and supports the concept of a complex ethiology for this symptom. We conclude that this new behavioral system analysis associated with microdialysis study constitutes a powerful tool to investigate the role of different neurotransmitters in the occurrence of the behavioral components described in the HPNS of rats.

Many authors have demonstrated that electrolytic lesions of the median raphe nucleus lead to dramatic hyperactivity, but little is known as to the neural substrates of this effect. In the current series of experiments we investigated this question by examining locomotor activity and forebrain serotonin levels after the placement of wire knife cuts in various locations around the median raphe. Activity was measured in a five minute open field test and a one hour tilt cage test. Knife cuts designed to transect the major ascending serotonergic projections of the median raphe led to a pronounced depletion of forebrain serotonin, but had no effect on locomotor activity in either testing situation. Knife cuts located antero-ventral to the median raphe, designed to interrupt raphe connections with the ventral tegmental area and interpeduncular nucleus, increased activity in the tilt cage but not in the open field test. These cuts produced only small effects on forebrain serotonin levels. Knife cuts caudal to the median raphe failed to influence forebrain serotonin levels, but produced a significant increase in both open field and tilt cage activity. The effects of the posterior and the anteroventral cuts on tilt cage locomotion were additive, suggesting that different fiber systems were damaged by the two cuts. These results demonstrate that it is possible to double dissociate changes in forebrain serotonin levels and locomotor activity with lesions in the vicinity of the median raphe and further show that ascending projections are unlikely to be the only pathways involved in the effects of median raphe lesions on locomotor behavior.