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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 PCBexposed SD rats) were harvested at postnatal day 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 RAE 230 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.

Acquisition of discrete-trial lever-press avoidance learning was studied in three experiments. Experiment I compared a new training procedure, which produces rates of leverpress avoidance learning comparable to those obtained in shuttle boxes, with a "conventional", less efficient training procedure. A factorial design was used to compare continuous versus intermittent shock and a long-variable versus a short-fixed signal-shock interval. Learning was best in the groups trained with the long and variable interval and poorest in those trained with the short and fixed interval. Type of shock had no effect. Experiment II separated the effects of duration from those of variability of the signal-shock interval. Fixed and variable intervals of 10 and 60 sec were tested and duration was the only significant factor. Experiment III addressed the effect of the differential opportunity to avoid provided by long signal-shock intervals by varying this interval from 10 to 60 sec in 10-sec steps.Only the 10-sec group showed slow acquisition relative to the others. Analysis of avoidance response latencies showed that the distributions for all groups were positively skewed and that skewness increased with increasing duration of the signal-shock interval. At intervals longer than 20 sec, the animals made progressively less use of their increased opportunity to respond. The data do not support the opportunity-to-respond interpretation of the effects of duration of signal-shock interval and suggest that some type of inhibitory process may block lever-press avoidance learning at intervals as short as 10 sec. The significance of these findings for species-specific defense reaction and preparedness theories was emphasized.

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