The present study evaluates juvenile stroke-prone spontaneously hypertensive rats (SHRSP) as an animal model of a developmental disorder, which is diagnosed according to hyperactivity-impulsivity and/or inattention. To characterize behavioural alterations, we studied motor activity, as well as emotional and cognitive behaviours in juvenile SHRSP, with and without methylphenidate, a psychostimulant. Ambulatory and rearing activities in the open-field environment were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY). In the elevated plus maze task, the entries into open arms, as an index of impulsivity, were significantly increased in SHRSP. In the Y-maze task, spontaneous alternation behaviour, as an index of attention, was significantly lowered in the male SHRSP, but not in the female SHRSP, indicating that spontaneous alternation deficit is gender specific. Methylphenidate (0.01-1 mg/kg, i.p.) significantly attenuated locomotor hyperactivity at low doses and dose-dependently improved the spontaneous alternation deficit in SHRSP. Our findings reveal that juvenile SHRSP manifest problematic behaviours resembling a developmental disorder, attention-deficit/hyperactivity disorder (ADHD), namely hyperactivity-impulsivity and/or inattention. Methylphenidate alleviated the behavioural symptoms of hyperactivity and inattention. We propose that juvenile SHRSP are an appropriate animal model of a developmental disorder resembling ADHD, from behavioural and pharmacological perspectives.
SUMMARY In order to elucidate the behavioral changes related to stroke, ambulatory activity and water drinking were observed in stroke-prone spontaneously hypertensive rats (SHRSP). Age matched male SHRSP and Wistar Kyoto rats (WKY) were subjected to a 12 hour light and dark alternation cycle. Ambulation and drinking activity counts were determined simultaneously with an Ambulo-Drinkometer. Before stroke, ambulation and drinking activity counts in the dark phase (82%) were higher than those in the light phase (18%). Both parameters were well synchronized with the light and dark alternation cycle. With aging, daily ambulation decreased while daily drinking activity increased in SHRSP and WKY. Daily ambulation and drinking activity in 15 and 30 week old SHRSP were greater than those of WKY. It was demonstrated with an Ambulo-Drinkometer that SHRSP undergo specific behavioral changes before the onset of stroke. For instance, the 40-60 week old SHRSP showed significant individual variation in both ambulation and drinking activity. This desynchronization with the light and dark alternation cycle was followed by stroke. Twenty seven autopsies showed 11 cerebral infarctions, 10 cerebral hemorrhage and 6 cerebral hemorrhage with infarctions to be the causes of death. Stroke Vol 16, No 1, 1985 STROKES IN HUMANS occur abruptly due to underlying diseases including essential hypertension and cerebral artery sclerosis.' A retrospective analysis of stroke patients from the literature 2 -3 reveals that approximately 75% of the patients demonstrated cerebral infarctions and 11 % demonstrated cerebral hemorrhages. The lethal course of stroke in stroke-prone spontaneously hypertensive rats (SHRSP) established by Okamoto et al 4 coincides well with the lethal course of patients with cerebrovascular lesions.5 " 7 Yamori et al 5 has classified stroke-related behavioral changes in SHRSP from a symptomatical point of view. No reports are available in the literature, however, concerning the behavior of SHRSP during their entire life span. In order to identify prodromes of stroke, the present study was carried out to observe the behavioral pattern changes throughout the SHRSP life span (including the development period of hypertension, the onset of stroke and death). Thus, a chronobiological analysis of the behavioral changes in SHRSP was performed. MethodsWe used SHRSP and WKY donated by Prof. Dr. Okamoto, Department of Pathology, Kinki University School of Medicine. Age-matched male SHRSP and male WKY were subjected to a 12 hour light (L) and dark (D) alternation cycle (LD). Illumination was provided by fluorescent light (100 Lux). Room temperature was maintained at 22 ± 2°C throughout the experiment. Rats were fed a regular diet
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