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Hormones and behavior
08, 2022;144 105205.

Norepinephrine and dopamine contribute to distinct repetitive behaviors induced by novel odorant stress in male and female mice.

Daniel J Lustberg, Joyce Q Liu, Alexa F Iannitelli, Samantha O Vanderhoof, L Cameron Liles, Katharine E McCann, David Weinshenker
Author Information
  1. Daniel J Lustberg: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  2. Joyce Q Liu: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  3. Alexa F Iannitelli: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  4. Samantha O Vanderhoof: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  5. L Cameron Liles: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  6. Katharine E McCann: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  7. David Weinshenker: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: dweinsh@emory.edu.
PMID: 35660247 DOI: 10.1016/j.yhbeh.2022.105205

Abstract

Exposure to unfamiliar odorants induces an array of repetitive defensive and non-defensive behaviors in rodents which likely reflect adaptive stress responses to the uncertain valence of novel stimuli. Mice genetically deficient for dopamine β-hydroxylase (Dbh-/-) lack the enzyme required to convert dopamine (DA) into norepinephrine (NE), resulting in globally undetectable NE and supranormal DA levels. Because catecholamines modulate novelty detection and reactivity, we investigated the effects of novel plant-derived odorants on repetitive behaviors in Dbh-/- mice and Dbh+/- littermate controls, which have catecholamine levels comparable to wild-type mice. Unlike Dbh+/- controls, which exhibited vigorous digging in response to novel odorants, Dbh-/- mice displayed excessive grooming. Drugs that block NE synthesis or neurotransmission suppressed odorant-induced digging in Dbh+/- mice, while a DA receptor antagonist attenuated grooming in Dbh-/- mice. The testing paradigm elicited high circulating levels of corticosterone regardless of Dbh genotype, indicating that NE is dispensable for this systemic stress response. Odorant exposure increased NE and DA abundance in the prefrontal cortex (PFC) of Dbh+/- mice, while Dbh-/- animals lacked NE and had elevated PFC DA levels that were unaffected by novel smells. Together, these findings suggest that novel odorant-induced increases in central NE tone contribute to repetitive digging and reflect psychological stress, while central DA signaling contributes to repetitive grooming. Further, we have established a simple method for repeated assessment of stress-induced repetitive behaviors in mice, which may be relevant for modeling neuropsychiatric disorders like Tourette syndrome or obsessive-compulsive disorder that are characterized by stress-induced exacerbation of compulsive symptoms.

Keywords

Digging Dopamine Dopamine beta-hydroxylase (DBH) Grooming Nepicastat Norepinephrine Novelty stress Odorant Prefrontal cortex Repetitive behavior

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Grants

  1. R01 NS102306/NINDS NIH HHS
  2. RF1 AG061175/NIA NIH HHS
  3. T32 ES012870/NIEHS NIH HHS
  4. T32 NS007480/NINDS NIH HHS

MeSH Term

Animals
Dopamine
Dopamine beta-Hydroxylase
Mice
Norepinephrine
Odorants
Prefrontal Cortex

Chemicals

Dopamine beta-Hydroxylase
Dopamine
Norepinephrine
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 3

Word Cloud

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