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Attention deficit hyperactivity disorder (ADHD) is a serious behavioral syndrome seen in children, and more common in males than females. There is increasing evidence that prenatal and/or early life exposure to persistent organic pollutants (POP) such as polychlorinated biphenyls (PCB) is associated with increased risk of ADHD occurrence. While PCB exposure is usually attributed to ingestion of contaminated food, recent reports of elevated PCB concentrations in indoor air, especially in schools, raised concern regarding inhalation as an important route of exposure to PCB with consequent effects on neurobehavior. The effects of exposure to air contaminated with Aroclor 1248 or contaminated sediment (SED) from the St. Lawrence River were examined on operant behavior of male and female Sprague-Dawley rats. Data showed that relative to controls, vapor-phase inhalation of PCB, whether from blowing air over Aroclor 1248 or from blowing air over sediment contaminated with PCB, resulted in hyperactivity and impatience in rats, more pronounced in males than females. These results are consistent with the hypothesis that inhalation of PCB may contribute to behavioral abnormalities in children.

Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the spontaneously hypertensive rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar/Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal days (PNDs) 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real-time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11, and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc, and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1, and Hes6. The epigenetic genes Crebbp, Mecp2, and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms.

We examined whether exposure to polychlorinated biphenyls (PCBs) around puberty would produce hyperactivity and impulsiveness in adult Sprague–Dawley rats. Randomly assigned groups consumed food containing environmental concentrations of Aroclor 1248, PCB-contaminated St. Lawrence River carp, or corn oil (control). All received operant training to a final multiple (mult) 120-s, fixed interval (FI), 5-min extinction (EXT) schedule. Pressing rates of both exposed groups for drops of water averaged more than 1.5 times that of controls, especially toward the end of the 120-s interval. This overactivity included bursts with short (≤0.5 s) interresponse times (IRTs), behavior characteristic of hyperactive boys and genetically hyperactive rats. The exposed groups also overreacted to the decreases in reinforcement density associated with transition to the final schedule. The results were interpreted in terms of the possible alterations in the animals’ reinforcement mechanisms and the possible neurotoxic effects of PCB exposure.

The present study was aimed at determining whether the behaviour of the spontaneously hypertensive rat (SHR), an animal model of attention-deficit hyperactivity disorder (ADHD), showed sex differences parallel to those seen in ADHD children. The experimental protocol contained an operant discrimination task, a two-component multiple (mult) 2-min fixed interval (FI) 5-min extinction (EXT) schedule of water reinforcement, a reliable behavioural paradigm for testing activity levels, discrimination behaviour and impulsiveness. The results indicated that both male and female SHRs show some of the most important behavioural traits of ADHD. Both were hyperactive and showed discrimination problems in terms of a behavioural extinction deficit towards the end of the EXT component. Still their behaviour differed markedly, which was probably due to quite different underlying mechanisms. The behavioural characteristics of the female SHRs may be compatible with an attention-deficit interpretation, whereas the behavioural characteristics of the male SHRs may be due to a shorter than normal delay-of-reinforcement gradient. The present study strengthens the position of SHR as an animal model of ADHD for future studies that may elucidate details in the underlying neurobiological deficits and for testing various treatment strategies.

The relationship between performance in an avoidance conditioning paradigm and the plasma glucose levels of Sprague-Dawley rats was examined in two experiments. In Experiment 1 we investigated whether glucose levels varied with the animal's relative success at acquiring the avoidance task. Results indicated that animals classified as avoiders (60% avoidance and above) had lower glucose levels than animals classified as escapers (30% avoidance and below). In Experiment 2 we looked at whether glucose levels showed within-subject changes with avoidance acquisition. Results demonstrated that glucose levels showed reductions if an animal learned the avoidance response. Subjects that did not learn the response showed no such reduction. Such results suggest that the physiological response to stress is attenuated by acquisition of successful coping behaviors that exercise control over the onset of aversive events.

Two studies of variables affecting voluntary ethanol consumption by adolescent male and female rats are reported. Sprague–Dawley (SD) and spontaneously hypertensive rats (SHRs) were compared in Experiment 1. Starting on postnatal day 30 all had 24-h access to 2%, then 4%, and then 6% ethanol, followed by 1-h access to the 6% until intake stabilized. During the 1-h access SHR females consumed more ethanol than all other groups. In Experiment 2, the same procedure was used to compare SD groups prenatally exposed to nicotine, with controls. Nicotine-exposed females consumed more ethanol during 1-h access than both nicotine-exposed and control males; but after using water intake as a covariate, the differences were not significant. These data show that deprivation conditions need to be considered when generalizing the results of voluntary consumption studies, and that estrogens may be a modulator of addictive behavior.

Lead and polychlorinated biphenyls (PCBs) both cause a reduction of intelligence quotient and behavioral abnormalities in exposed children that have features in common with attention deficit hyperactivity disorder. We have used rats as a model to study the effects of both perinatal and acute exposure to lead or PCBs in an effort to compare and understand the mechanisms of these nervous system decrements. Long-term potentiation (LTP) is an electrophysiologic measurement that correlates well with cognitive ability. We have determined the effects of chronic perinatal exposure to lead or PCB 153 as well as acute application of these substances to isolated brain slices, with recordings in two areas of the hippocampus, CA1 and CA3. Both substances, whether chronically or acutely applied, significantly reduced LTP in CA1 in animals at age 30 and 60 days. In CA3, they reduced LTP in 30-day animals but potentiated it in 60-day animals. Although neither lead nor PCB 153 alters baseline synaptic transmission at low stimulus strengths, at higher levels they induce changes in the same direction as those of LTP. These results show surprisingly similar actions of these quite different chemicals, and the similarity of effects on chronic and acute application indicates that effects are both pharmacologic and developmental. Behavioral studies of rats exposed to PCBs from contaminated fish show hyperactivity, impulsiveness, and increased frustration relative to unexposed controls. These results demonstrate that lead and PCBs have similar effects on synaptic plasticity and behavior and suggest that the compounds may act through a common mechanism.

PCBs have been considered to be almost nonvolatile and insoluble in water. However, recent studies have shown the importance of their slight solubility in water and capability to enter the atmosphere and disperse throughout the global environment. This preliminary study was designed to measure uptake and observe any physiological changes in Sprague-Dawley rats. The PCB product Aroclor 1242 is the major pollutant of the Hudson River, NY, and New Bedford Harbor, MA. The rats were exposed for 30 d to 0.9 microg/m3 via inhalation and 0.436 microg/g (ppm) in the food. The inhalation of PCBs gave a greater PCB uptake than ingestion. Both routes of administration caused significant serum thyroid hormone elevations. Histopathologic changes were observed in the urinary bladder, thymus, and the thyroid after both exposure regiments. Rearing and ambulation were significantly decreased in both exposure regiments in an open field behavior test.

The aim of this study was to trace by molecular imaging techniques the neural substrates of attention deficit hyperactivity disorder (ADHD) using the spontaneously hypertensive rat (SHR) as animal model. Adult SHR and Wistar-Kyoto (WKY) controls were used throughout this study. In experiment 1, naive male SHR and WKY were used, whereas in experiment 2 SHR and WKY rats of both genders were trained on a multiple fixed interval (FI (120 s for water, 5-min extinction)) paradigm and sacrificed 6 months later. In both experiments coronal sections of the anterior forebrain were processed for quantitative cytochrome oxidase (COase) histochemistry by the method of Gonzalez-Lima. Optical density values were transformed into actual enzyme activity units by using tissue-calibrated standards. In experiment 1, non-trained male rats of the SHR line showed lower COase activity in the medial and lateral prefrontal cortices, compared with WKY controls. In experiment 2, there was a line x treatment interaction effect in the pole of the nucleus accumbens (ACB). Regional correlative analyses revealed that: (i) under basal conditions, SHR are more synchronized than WKY rats in the COase level of different brain regions; and (ii) the training desynchronizes COase activity in the WKY, further synchronizes it and increases the cross-talk between hemispheres in male SHR only. Neurobehavioral covariations between behavioural scores and metabolic capacity in the medial and lateral prefrontal/frontal cortices, the caudate-putamen complex (CPU), the pole, core, and shell of the accumbal complex (ACB), and the ventral pallidum (VP), indicated that, in the WKY rats, the frequency of lever pressing covaried positively with the COase activity in the CPU, whereas in the SHR covaried with both medial and lateral prefrontal/frontal cortices. The bursts of activity during the 1-1.33-s segment was positively correlated, in the WKY rats only, with the core and shell of the ACB, and with the VP. Finally, the correlative profiles showed significant gender differences with effects in male SHR only. Thus, the results lend support to the involvement of the cortico-striato-pallidal system in ADHD.

Lever-press avoidance performances of Spontaneously Hypertensive (SHR) and Wistar-Kyoto (WKY) rats were observed in two experiments. The first compared them at shock intensities of 1 or 2 mA. The SHRs had the highest percentage of avoidances, made the most coping responses (avoidances plus escapes), and received the fewest shocks (ps less than .05). They also had shorter avoidance and initial-escape latencies (ps less than .05). In the second experiment these strains were trained with signal-shock intervals that produce good (60 s) or poor (10 s) avoidance acquisition. Analysis of the Strain x Conditions x Blocks interaction showed that SHRs performed better with the longer interval (p less than .05), whereas WKYs' performance was similar with both (p greater than .05). Thus WKYs differed from all other strains previously exposed to these conditions. The findings are interpreted in terms that emphasize the SHRs' tendency to move, compared with the WKYs' tendency to freeze in response to aversive stimuli, rather than characterizing SHRs as hyperreactive.

The plasma cholesterol concentrations of rats receiving either lever-press escape or avoidance training, exposure to unpredictable, uncontrollable grid shocks using a yoked procedure, or no shocks, were compared in two experiments. All were fed a cholesterol-supplemented diet prior to and during the 30 days of exposure to these differing stress treatments. The results of both experiments showed that yoked groups had higher terminal levels of cholesterol than their experimental counterparts in the escape or avoidance group even though they received the same amounts of aversive stimulation and ate the same amounts of the diet. Both were higher than the nonshocked groups when the amount of food intake for all was matched in Experiment 2. The type of level-press training had no effect.

The effects of differential psychological stress on serum triglyceride and aortic cholesterol levels were investigated in two experiments. In the first, rats with an unknown infant handling history purchased as adults from a standard supplier were subjected to predictable, controllable shocks; unpredictable, uncontrollable shocks; or the apparatus or their home cages with no shocks, for 30 days. All were maintained on a cholesterol-supplemented diet except during the daily 51-min stress sessions. The amounts eaten were equated among the groups. The results that the shocked rats had significantly lower terminal levels of serum triglycerides, and those receiving unpredictable, uncontrollable shocks had significantly less aortic cholesterol, than the nonshocked groups, which did not differ from each other in either measure. In the second experiment, rats born in this laboratory were either handled or left undisturbed in infancy and were exposed to a diet and differential stress conditions as adults. Animals handled in infancy had significantly lower aortic cholesterol than nonhandled animals across all stress conditions. In addition, those exposed to unpredictable, uncontrollable shocks had lower aortic cholesterol than those exposed to predictable, controllable shocks, and both had lower aortic cholesterol than the nonshocked group. Similar differential stress effects across stress conditions were seen in all the rats' serum triglyceride levels in Experiment 2. The effects of infantile handling did not interact with the stress effects, and neither could be accounted for by group differences in amount of the diet eaten or weight gained.

Female Sprague-Dawley rats were either ovariectomized or sham-operated prior to puberty. As adults, they were maintained on a cholesterol-supplemented diet and subjected to either predictable, controllable shock; unpredictable, uncontrollable shock; or no shock for 30 days (51-min daily sessions). Sham-operated rats had higher plasma cholesterol levels than ovariectomized rats, but neither group showed an effect of stress treatments. For both groups, serum triglyceride and aortic cholesterol levels were lower in stressed than nonstressed rats. Additionally, the ovariectomized rats had higher levels of serum triglycerides than sham-operated controls.

Rats, fed a 1% cholesterol diet, were subjected to either predictable, controllable shock; unpredictable, uncontrollable shock; or no shock for 30 days (51-min daily sessions). Half of the rats in each condition were allowed access to a running wheel for 3 hr immediately after each stress session except for the final stress session. Immediately following the final stress session, animals were sacrificed and blood and aorta samples were taken. Stressed animals allowed to run showed lower plasma corticosterone levels than stressed animals not allowed to run. Overall, stressed animals had lower levels of aortic cholesterol than nonstressed animals. Whereas running resulted in decreased levels of plasma cholesterol, aortic cholesterol levels were higher for the running animals than for the nonrunning animals.