Regular article
The spontaneously hypertensive rat as an animal model of attention-deficit hyperactivity disorder: Effects of methylphenidate on exploratory behavior

https://doi.org/10.1016/0163-1047(90)90848-ZGet rights and content

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.

References (37)

  • American Psychiatric Association
  • BlanchardR.J. et al.

    Defensive reactions and exploratory behavior in rats

    Journal of Comparative and Physiological Psychology

    (1974)
  • ConnersC.K.

    Recent drug studies with hyperkinetic children

    Journal of Learning Disabilities

    (1971)
  • DewsP.B.

    Studies on behavior. IV. Stimulant actions of methamphetamine

    Journal of Pharmacology and Experimental Therapeutics

    (1958)
  • Gittelman KleinR. et al.

    The role of psychostimulants and psychosocial treatments in hyperkinesis

  • JaffeJ.H.

    Drug addiction and drug abuse

  • KuczenskiR.

    Biochemical actions of amphetamine and other stimulants

  • LyonM. et al.

    The action of central nervous system stimulant drugs: A general theory concerning amphetamine effects

  • Cited by (123)

    • The effects of early life stress on impulsivity

      2022, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      In humans, low levels of DAT, which could increase DA signaling, are associated with poor inhibitory control (Kim, 2018; Sekiguchi et al., 2019; Smith et al., 2018). ELS manipulations can be combined with animal models which are thought to capture aspects of psychiatric disease, such as the spontaneously hypertensive rat (SHR), which has features of ADHD, including inattention, impulsivity, and hyperactivity (Knardahl and Sagvolden, 1979; Russell et al., 2005; Sagvolden, 2000; Sagvolden et al., 2005; Wultz et al., 1990). Maternal separation in SHR increases the rate of DA clearance in the ventral striatum (Womersley et al., 2011).

    View all citing articles on Scopus
    1

    The authors gratefully ackowledge Mr. Geir Sagvolden for programming assistance.

    View full text