Acute intranasal dopamine application counteracts the reversal learning deficit of spontaneously hypertensive rats in an attentional set-shifting task

Jay Shake Li, Shan Sung Yang, Joseph P. Huston, Yuan Hsin Chao, Yi Mei Yang, Claudia Mattern

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: Studies on the attention-deficit/hyperactivity disorder (ADHD) have concluded that the disorder might be caused by a deficit in the inhibitory control of executive functions because of dopamine hypofunction. Recently, the intranasal route has emerged as an effective alternative means for sending dopamine directly to the brain. However, whether the treatment can ameliorate the deficits of inhibitory control in ADHD remains unknown. Objectives: Investigating the effects of acute intranasal dopamine (IN-DA) on the inhibitory control of executive functions of an ADHD rodent model. Methods: We trained an animal model of ADHD, the spontaneously hypertensive rat (SHR), and Wistar rats as controls, in an attentional set-shifting task (ASST) in which dopamine (0.15 mg/kg, 0.3 mg/kg, or vehicle) was intranasally administered before the final test. Results: IN-DA application dose-dependently improved the performance and reduced errors of SHR in the initial reversal learning. The effect size was comparable to that of a peripheral injection of 0.6 mg/kg methylphenidate. In control Wistar rats, the highest dose of intranasal dopamine (0.3 mg/kg) induced deficits in the reversal learning of extradimensional discriminations. Conclusions: The findings suggest that the IN-DA treatment has potential for use in the treatment of ADHD; however, caution must be exercised when determining the dosage to be administered, because too much dopamine may have negative effects.

Original languageEnglish (US)
Pages (from-to)2419-2428
Number of pages10
JournalPsychopharmacology
Volume238
Issue number9
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
This work was supported by the German National Science Foundation [DFG] grant HU 306/27–3 and by the University of Minnesota faculty start-up fund to YMY.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • ADHD
  • Dopamine
  • Intranasal administration
  • Reversal learning
  • SHR

PubMed: MeSH publication types

  • Journal Article

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