title: Naloxone exacerbates memory impairments and depressive-like behavior after mild traumatic brain injury (mTBI) in mice with upregulated opioid system activity.
abstract: The neuroprotective role of the endogenous opioid system in the pathophysiological sequelae of brain injury remains largely ambiguous. Noteworthy, almost no data is available on how its genetically determined activity influences the outcome of mild traumatic brain injury. Thus, the aim of our study was to examine the effect of opioid receptor blockage on cognitive impairments produced by mild traumatic brain injury in mice selectively bred for high (HA) and low (LA) swim-stress induced analgesia that show innate divergence in opioid system activity. Mild traumatic brain injury was induced with a weight-drop device on anaesthetized mice. Naloxone (5mg/kg) was intraperitoneally delivered twice a day for 7days to non-selectively block opioid receptors. Spatial memory performance and manifestations of depressive-like behavior were assessed using the Morris Water Maze and tail suspension tests, respectively. Mild traumatic brain injury resulted in a significant deterioration of spatial memory performance and severity of depressive-like behavior in the LA mouse line as opposed to HA mice. Opioid receptor blockage with naloxone unmasked cognitive deficits in HA mice but was without effect in the LA line. The results suggest a protective role of genetically predetermined enhanced opioid system activity in suppression of mild brain trauma-induced cognitive impairments. Mice selected for high and low swim stress-induced analgesia might therefore be a useful model to study the involvement of the opioid system in the pathophysiology and neurological outcome of traumatic brain injury.
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Banacha 1B, 02-097 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lesniak
authors.affiliation: Department of Genomics, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Postepu 36A, 05-552 Magdalenka, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Leszczynski
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Banacha 1B, 02-097 Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bujalska-Zadrozny
authors.affiliation: Department of Anatomy, and Anthropology, Sackler Faculty of Medicine, and Sagol School of Neuroscience, Tel Aviv University, Ramat-Aviv, 69978 Tel Aviv, Israel.
authors.forename: Chaim G
authors.initials: CG
authors.lastname: Pick
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Banacha 1B, 02-097 Warsaw, Poland; Department of Internal Medicine, Hypertension and Vascular Diseases, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland; Department of Genomics, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Postepu 36A, 05-552 Magdalenka, Poland. Electronic address: msacharczuk@wum.edu.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Sacharczuk
mesh_terms: D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001924:Brain Concussion / Q000503:physiopathology*; D003863:Depression / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000066829:Neuroprotection / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects*; D065852:Spatial Memory / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone
keywords: Depressive-like behavior; HA/LA mice; Memory impairments; Mild traumatic brain injury; Opioid system