Methylphenidate improves spatial memory of spontaneously hypertensive rats: Evidence in behavioral and ultrastructural changes

The purpose of this study was to investigate the effects of methylphenidate on the spatial learning and memory ability and synaptic ultrastructure in the hippocamal CA3 region of the spontaneously hypertensive rat, a rat model of attention deficit hyperactivity disorder. The methylphenidate group and model group were respectively administered the drug (10 mg/kg, i.p.) and saline 30 min before place navigation on 6 consecutive days, a control group of Wistar Kyoto rats were administered saline in the same way. Transmission electron microscopic and imaging analyses were then used to detect and analyze any microstructural changes. The performance of the model rats treated with the drug was the best in the probe test. In addition, three parameters including the length of the active zone, the thickness of the postsynaptic density and the synaptic curvature were measured to show the significant synaptic configuration changes in the methylphenidate group in comparison to the model group. Therefore, these ultrastructural changes in the hippocampal CA3 region may be one of the mechanisms by which methylphenidate improves the spatial memory ability of spontaneously hypertensive rats. The Wistar Kyoto rats showed a significantly decreased latency for finding the platform from the second day in spite of a floating characteristic, while in the probe test, their performance was close to that of the model rats. Finally, morphological evidence suggested the model rats to have a cognitive impairment in comparison to the control group and their better performance was possibly due to the physiological hyper-response of WKY in the water maze tasks.