title: A2 noradrenergic neurons regulate forced swim test immobility.
abstract: The Wistar-Kyoto (WKY) rat is a widely used animal model of depression, which is characterized by dysregulation of noradrenergic signaling. We previously demonstrated that WKY rats show a unique behavioral profile on the forced swim test (FST), characterized by high levels of immobility upon initial exposure and a greater learning-like response by further increasing immobility upon re-exposure than the genetically related Wistar rats. In the current study we aimed to determine whether altered activation of brainstem noradrenergic cell groups contributes to this behavioral profile. We exposed WKY and Wistar rats, to either 5min of forced swim or to the standard two-day FST (i.e. 15min forced swim on Day 1, followed by 5min on Day 2). We then stained their brains for FOS/tyrosine hydroxylase double-immunocytochemistry to determine potential differences in the activation of the brainstem noradrenergic cell groups. We detected a relative hyperactivation in the locus coeruleus of WKY rats when compared to Wistars in response to both one- and two-day forced swim. In contrast, within the A2 noradrenergic cell group, WKY rats exhibited diminished levels of FOS across both days of the FST, suggesting their lesser activation. We followed up these observations by selectively lesioning the A2 neurons, using anti-dopamine-β-hydroxylase-conjugated saporin, in Wistar rats, which resulted in increased FST immobility on both days of the test. Together these data indicate that the A2 noradrenergic cell group regulates FST behavior, and that its hypoactivation may contribute to the unique behavioral phenotype of WKY rats.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, United States.
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Nam
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Virginia Tech Carilion School of Medicine, United States; School of Neuroscience, Virginia Tech, United States. Electronic address: iakerman@carilionclinic.org.
authors.forename: Ilan A
authors.initials: IA
authors.lastname: Kerman
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003866:Depressive Disorder / Q000473:pathology*; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000502:physiology*; D000922:Immunotoxins / Q000627:therapeutic use; D008297:Male; D008845:Microinjections; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D017552:Solitary Nucleus / Q000187:drug effects / Q000473:pathology; D013045:Species Specificity; D013550:Swimming / Q000523:psychology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000922:Immunotoxins; D016761:Oncogene Proteins v-fos; D054789:Ribosome Inactivating Proteins, Type 1; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D000076985:Saporins
keywords: Behavior; Depression; Forced swim test; Fos; Rat