Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder.

BACKGROUND: Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. METHODS: This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. RESULTS: The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. CONCLUSIONS: The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.

Effects of different adrenergic blockades on the stress resistance of Wistar rats.

The coordinated responses of the sympathoadreno-medullary (SAM) system and hypothalamic-pituitary-adrenal (HPA) axis could improve the organism's capacity to cope with stress, but its underlying mechanism is still unclear. In the present study, 32 Wistar rats were employed and divided into four groups: control, CUMS, PROP and PRAZ. After the chronic unpredicted mild stress (CUMS) model was built in the latter three groups, all animals were exposed to inescapable footshock. We found that α(1)-adrenoceptor antagonist prazosin (PRAZ) administration could improve behavior changes, reduce the cellular impairment in brain and inhibit the hyperfunction of HPA axis induced by CUMS exposure. Moreover, it decreased the heat shock protein 70 and inducible nitric oxide synthase expression in different brain areas as subsequently exposed to acute stress. In conclusion, α1-adrenoceptor may play a major role in regulating the coordinated responses between two physiological axes and improve the stress resistance.

Effects of adrenergic agents on stress-induced brain microstructural and immunochemical changes in adult male Wistar rats.

This preliminary study aims to explore how adrenergic agents modulate stress response and affect stress-induced behavioral and brain changes in rodents. A total of 40 adult male Wistar rats were subjected to chronic unpredictable mild stress (CUMS) and randomly divided into five groups. At 30 min before daily stress exposure, the rats were intraperitoneally injected with phentolamine (5mg/kg), noradrenalin (1.0mg/kg), propranolol (10mg/kg), isoproterenol (0.05 mg/kg) or saline, respectively. Another 8 rats served as normal control and received daily saline injection without stress exposure. Open-field behaviors were tested at 1 day after the end of the 21 days of stress exposure. Blood samples were collected for serum corticosterone measurement. Brain sections containing hippocampus were stained with hematoxylin and eosin (H&E) as well as by immunohistochemistry for heat shock protein 70 (hsp70) and nitric oxide synthase type 2 (nos2) analyses. The experimental results demonstrated that repetitive dosing of noradrenalin, phentolamine, and propranolol during chronic stress might region-dependently attenuate stress-induced microstructural and biochemical changes in the hippocampus, although propranolol intensified stress-induced behavioral changes.

Swimming exercise effects on the expression of HSP70 and iNOS in hippocampus and prefrontal cortex in combined stress.

Exercise could play a beneficial role in stress, but its underlying mechanism especially about heat shock protein 70 (HSP70) and inducible nitric oxide synthase (iNOS) in brain has not been fully clarified. Moreover, few studies have investigated swimming exercise and its effects on the combined stress of both chronic and acute stress. In this study we tried to investigate the role of swimming exercise in combined stress and whether its biological mechanism was related to the HSP70 and iNOS in hippocampus and prefrontal cortex. 32 Wistar rats were enrolled and divided into four groups: control, CUMS, labetalol and exercise. After the animal model of chronic unpredicted mild stress (CUMS) was built in the latter three groups, all the rats were given the novel acute stress of inescapable footshock. The behavioral changes were measured by open field test. Radioimmunoassay (RIA) was adopted to test the change of serum corticosterone (CORT). The expression of HSP70 and iNOS in hippocampus and prefrontal cortex was analyzed by Western blot. The results demonstrated that swimming exercise could not only improve the behavior changes and protect the function of HPA axis stable in CUMS animals exposed to novel acute stress, but also increase the HSP70 expression and decrease the iNOS expression in hippocampus and prefrontal cortex. In conclusion, swimming exercise could play a beneficial role in combined stress by up-regulating HSP70 level and down-regulating iNOS level in brain.