David F. Berger

Sex differences in operant discrimination behaviour in an animal model of attention-deficit hyperactivity disorder.

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.

A Comparison of Molecular Alterations in Environmental and Genetic Rat Models of ADHD: a pilot study

Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in school‐aged children. In addition to genetic factors, environmental influences or gene × 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.

The relationship between plasma corticosterone levels and leverpress avoidance vs. escape behaviors in rats

Groups of rats were exposed to training procedures that produce leverpress avoidance (Experiment 1) or escape (Experiment 2) behaviors. Plasma samples were obtained by decapitation after 30 sessions, and corticosterone concentrations were determined and compared with those of corresponding yoked and nonshocked (time-in-box) groups. The mean corticosterone level of the “avoiders” was lower than that of their yoked mates and not different from that of their non-shocked mates. This indicated a reduction in their arousal level with mastery of the avoidance response, which could not be accounted for by the reduction in numbers of shocks received. The mean corticosterone level of the “escapers” was as high as that of their yoked mates, and both levels were higher than that of the nonshocked group.

Effects of stress and exercise on plasma corticosterone, plasma cholesterol, and aortic cholesterol levels in rats.

&NA; 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.

AROCLOR 1242 INHALATION AND INGESTION BY SPRAGUE-DAWLEY RATS

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 effects of differential psychological stress on plasma cholesterol levels in rats.

&NA; 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.

An Animal Model of Attention Deficit Disorder

The main objective of the present study was to characterize sex differences in the temporal discrimination and activity level of an animal model of attention deficit disorder (ADD) using a conjunctive 120-s variable interval 16-s differential reinforcement of low rate (VIDRL) schedule of reinforcement. The results showed that the spontaneously hypertensive (SHR) male was generally hyperactive and that the SHR female was both hyperactive and had severe time discrimination problems. The latter caused relatively fewer reinforcers to be delivered. However, even when a reinforcer was delivered, the SHR female frequently failed to collect it. When the SHR females were in diestrus, their behavior became even less efficient. The present findings with the animal model seem to be in general agreement with the behavior of ADD children when a DRL schedule is used. Most of our results were explained as due to impulsiveness, which is more pronounced in the SHR female than in the male. In addition, the SHR female had at...

Effects of stress and ovariectomy on the plasma cholesterol, serum triglyceride, and aortic cholesterol levels of female rats

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.

Inhalation of Polychlorinated Biphenyls (PCB) Produces Hyperactivity in Rats.

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.

The effects of strain and prenatal nicotine exposure on ethanol consumption by adolescent male and female rats

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.