Effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on spontaneously hypertensive rats, an animal model of attention-deficit/hyperactivity disorder

Int J Dev Neurosci. 2016 Oct:53:83-89. doi: 10.1016/j.ijdevneu.2016.07.006. Epub 2016 Jul 25.

Abstract

The current treatment of choice for attention deficit hyperactivity disorder (ADHD) is pharmacotherapy. A search for new treatment options is underway, however, as the wide application of drugs to the general population of patients with ADHD is limited by side effects and the variance of pharmacokinetic effects of the drugs in each patient. In the present study, we applied repetitive transcranial magnetic stimulation (rTMS), a non-invasive treatment used in a number of other psychiatric disorders, to spontaneously hypertensive rats (SHRs), an animal model of ADHD, in order to assess the efficacy of the treatment in modifying behavioural symptoms as well as levels of dopamine, noradrenaline, serotonin, and brain-derived neurotrophic factor (BDNF). A total of fifteen sessions of high-frequency rTMS treatment were administered. Behavioural symptoms were observed using open field, Y-maze, and elevated plus-maze tests. Upon completion of the experiments, rats were sacrificed, and the neurochemical changes in brain tissue were analysed using high performance liquid chromatography and Western blotting. The SHRs treated with rTMS tended to exhibit less locomotor activity in the open field test over the course of treatment, but there was no improvement in inattention as measured by the Y-maze test. Furthermore, BDNF concentration increased and noradrenaline concentration decreased in the prefrontal cortex of SHRs treated with rTMS. The results of the present preclinical study indicate that rTMS may constitute a new modality of treatment for patients with ADHD, through further evaluation of specific treatment parameters as well as safety and efficacy in humans are required.

Keywords: Attention-deficit hyperactivity disorder (ADHD); Behavior analysis; Brain-derived neurotrophic factor (BDNF); Catecholamines; Repetitive transcranial magnetic stimulation (rTMS); Spontaneously hypertensive rat (SHR).

MeSH terms

  • Animals
  • Animals, Newborn
  • Attention Deficit Disorder with Hyperactivity / therapy*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Central Nervous System Stimulants / adverse effects
  • Chromatography, High Pressure Liquid
  • Exploratory Behavior / drug effects
  • Male
  • Maze Learning / drug effects
  • Methylphenidate / adverse effects
  • Neurotransmitter Agents / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Time Factors
  • Transcranial Magnetic Stimulation / methods*

Substances

  • Brain-Derived Neurotrophic Factor
  • Central Nervous System Stimulants
  • Neurotransmitter Agents
  • Methylphenidate