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Altered Activity in Efferent Projection Sites of the Brain Orexin System is Associated with Poor Cardiovascular Adaptability in an Animal Model of Hypertension and Attention Deficit/Hyperactivity Disorder (ADHD)

The neuropeptide orexin has recently been shown to be dysregulated in the spontaneously hypertensive rat (SHR), an animal model of essential hypertension. The SHR has also been proposed as a model of ADHD. The present study was undertaken to determine whether regional differences in brain activation could be linked to differences in behavior or cardiovascular reactivity in the SHR when compared to normotensive rats (WKY; n=3–10/group). Manganese‐enhanced MRI of naïve animals identified that multiple efferent projection sites of the orexin system, including the hippocampus (CA1 and CA3, P<0.01) and the midbrain (central gray, dorsal raphe, ventral tegmental nucleus) had significantly (P<0.05) lower activity in the SHR vs WKY, with the exception of locus coeruleus which had elevated activity (P<0.02). In object recognition and social interaction tests, the SHRs generally spent less time interacting than WKYs. On the elevated plus maze test, SHR spent twice the time in the open arm field. This was paralleled by a similar initial rise in blood pressure (22+/−1 mmHg) and heart rate between strains (165+/−10 bpm). By the end of the 5 minute test however, WKY values returned to baseline while the SHR blood pressure remained elevated (+3 vs +20 mmHg). These results support the link between heightened activity in locus coeruleus (a primary target of the orexin system), hypertension, and behavioral markers of ADHD, and raise a novel prospect that reduced activity in other midbrain regions may also be linked to altered system function/adaptation in the SHR.