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Open AccessArticle

Rats Lacking Dopamine Transporter Display Increased Vulnerability and Aberrant Autonomic Response to Acute Stress

1
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
2
Institute of Translational Biomedicine, St. Petersburg State University, Universitetskaya Emb. 7–9, 199034 St. Petersburg, Russia
3
St. Petersburg University Hospital, St. Petersburg State University, Universitetskaya Emb. 7–9, 199034 St. Petersburg, Russia
4
Department of Neurology and Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 842; https://doi.org/10.3390/biom10060842
Received: 26 March 2020 / Revised: 26 May 2020 / Accepted: 27 May 2020 / Published: 31 May 2020
(This article belongs to the Special Issue Dopamine Receptor in Health and Diseases)
The activity of the hypothalamus–pituitary–adrenal (HPA) axis is pivotal in homeostasis and presides the adaptative response to stress. Dopamine Transporter (DAT) plays a key role in the regulation of the HPA axis. We used young adult female DAT Knockout (KO) rats to assess the effects of DAT ablation (partial, heterozygous DAT+/-, or total, homozygous DAT-/-) on vulnerability to stress. DAT-/- rats show profound dysregulation of pituitary homeostasis, in the presence of elevated peripheral corticosterone, before and after acute restraint stress. During stress, DAT-/- rats show abnormal autonomic response at either respiratory and cardiovascular level, and delayed body temperature increase. DAT+/- rats display minor changes of hypophyseal homeostatic mechanisms. These rats display a similar pituitary activation to that of the control animals, albeit in the presence of higher release of peripheral corticosterone than DAT-/- after stress, and reduced temperature during stress. Our data indicate that DAT regulates the HPA axis at both the central and peripheral level, including autonomic function during stress. In particular, the partial deletion of DAT results in increased vulnerability to stress in female rats, which display central and peripheral alterations that are reminiscent of PTSD, and they might provide new insights in the pathophysiology of this disorder. View Full-Text
Keywords: dopamine transporter; stress; pituitary gland; HPA axis; autonomic response; post-traumatic stress disorder (PTSD) dopamine transporter; stress; pituitary gland; HPA axis; autonomic response; post-traumatic stress disorder (PTSD)
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MDPI and ACS Style

Illiano, P.; Bigford, G.E.; Gainetdinov, R.R.; Pardo, M. Rats Lacking Dopamine Transporter Display Increased Vulnerability and Aberrant Autonomic Response to Acute Stress. Biomolecules 2020, 10, 842.

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