Wultz B, Sagvolden T, Moser E I, Moser M B
Institute of Neurophysiology, University of Oslo, Norway.
Behav Neural Biol. 1990 Jan;53(1):88-102. doi: 10.1016/0163-1047(90)90848-z.
Spontaneously hypertensive rats (SHR) show a pervasive hyperactivity in several paradigms. Thus, these rats may be used as an animal model of childhood hyperactivity also called Attention-Deficit Hyperactivity Disorder. This disorder is frequently treated with psychomotor stimulant drugs, but little is known about the effects of such drugs on behavior. The present study investigated the behavioral effects of 1-24 mg/kg methylphenidate (Ritalin) on the exploratory behavior of male SHR and Wistar-Kyoto control rats (WKY) in a two-compartment free-exploration open field. Except following very high doses. SHR spent most of the session time in the field while WKY stayed in the home cage. Low and medium doses were followed by increased activity in the field for SHR and increased activity in the cage for WKY. The response-stimulatory effects of low to medium doses of methylphenidate are less in SHR than in WKY. Starting at medium doses, activity decreased and stereotyped behavior increased progressively by increasing dose. Locomotor activity in the field decreased following lower doses than locomotor activity in the cage, and vertical activity (rearing) was reduced by lower doses than horizontal activity (crossing). The following conclusions were drawn. (i) There is no "paradoxical" inhibition of SHR hyperactivity following methylphenidate. On the contrary, SHR activity is in fact stimulated, albeit to a lesser degree than that of WKY. (ii) The stimulatory effects of low to medium doses are, in general, most pronounced for the kind of exploratory behavior most frequently used by the rat during baseline conditions. (iii) Rearing might be more susceptible to adverse effects of methylphenidate than ambulation.
自发性高血压大鼠（SHR）在多种实验范式中均表现出普遍的多动。因此，这些大鼠可用作儿童多动（也称为注意力缺陷多动障碍）的动物模型。这种疾病通常用精神运动性兴奋药物治疗，但对于此类药物对行为的影响知之甚少。本研究在两室自由探索旷场中，研究了1 - 24 mg/kg哌甲酯（利他林）对雄性SHR和Wistar - Kyoto对照大鼠（WKY）探索行为的影响。除了极高剂量外，SHR在旷场中花费了大部分实验时间，而WKY则待在笼中。低剂量和中等剂量的哌甲酯使SHR在旷场中的活动增加，使WKY在笼中的活动增加。低至中等剂量的哌甲酯对SHR的反应刺激作用比对WKY的作用小。从中等剂量开始，活动减少，刻板行为随剂量增加而逐渐增加。旷场中的运动活动在较低剂量时比笼中的运动活动下降得更多，垂直活动（站立）在比水平活动（穿越）更低的剂量时就减少了。得出了以下结论。（i）哌甲酯给药后，SHR的多动没有出现“反常”抑制。相反，SHR的活动实际上受到了刺激，尽管程度比WKY小。（ii）一般来说，低至中等剂量的刺激作用对于大鼠在基线条件下最常使用的那种探索行为最为明显。（iii）站立可能比行走更容易受到哌甲酯不良反应的影响。
