Manipulation of vocal communication and anxiety through pharmacologic modulation of norepinephrine in the Pink1-/- rat model of Parkinson disease

Jesse D. Hoffmeister, Cynthia A. Kelm-Nelson, Michelle R. Ciucci

Research output: Contribution to journalArticlepeer-review

Abstract

Vocal deficits and anxiety are common, co-occurring, and interacting signs of Parkinson Disease (PD) that have a devastating impact on quality of life. Both manifest early in the disease process. Unlike hallmark motor signs of PD, neither respond adequately to dopamine replacement therapies, suggesting that their disease-specific mechanisms are at least partially extra-dopaminergic. Because noradrenergic dysfunction is also a defining feature of PD, especially early in the disease progression, drug therapies targeting norepinephrine are being trialed for treatment of motor and non-motor impairments in PD. Research assessing the effects of noradrenergic manipulation on anxiety and vocal impairment in PD, however, is sparse. In this pre-clinical study, we quantified the influence of pharmacologic manipulation of norepinephrine on vocal impairment and anxiety in Pink1-/- rats, a translational model of PD that demonstrates both vocal deficits and anxiety. Ultrasonic vocalization acoustics, anxiety behavior, and limb motor activity were tested twice for each rat: after injection of saline and after one of three drugs. We hypothesized that norepinephrine reuptake inhibitors (atomoxetine and reboxetine) and a β receptor antagonist (propranolol) would decrease vocal impairment and anxiety compared to saline, without affecting spontaneous motor activity. Our results demonstrated that atomoxetine and reboxetine decreased anxiety behavior. Atomoxetine also modulated ultrasonic vocalization acoustics, including an increase in vocal intensity, which is almost always reduced in animal models and patients with PD. Propranolol did not affect anxiety or vocalization. Drug condition did not influence spontaneous motor activity. These studies demonstrate relationships among vocal impairment, anxiety, and noradrenergic systems in the Pink1-/- rat model of PD.

Original languageEnglish (US)
Article number113642
JournalBehavioural Brain Research
Volume418
DOIs
StatePublished - Feb 10 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health [National Institute of Deafness and other Communication Disorders T32 DC009401 ; National Institute of Deafness and other Communication Disorders, R01 DC014358 ; National Institute of Deafness and other Communication Disorders R01 DC018584-01A1 ].

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • anxiety
  • norepinephrine
  • Parkinson Disease
  • Pink1
  • rat
  • ultrasonic vocalization

PubMed: MeSH publication types

  • Journal Article

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