Naloxone exacerbates memory impairments and depressive-like behavior after mild traumatic brain injury (mTBI) in mice with upregulated opioid system activity

Anna Lesniak, Pawel Leszczynski, Magdalena Bujalska-Zadrozny, Chaim G. Pick, Mariusz Sacharczuk

Research output: Contribution to journalArticlepeer-review

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 (5 mg/kg) was intraperitoneally delivered twice a day for 7 days 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.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalBehavioural Brain Research
Volume326
DOIs
StatePublished - 30 May 2017

Keywords

  • Depressive-like behavior
  • HA/LA mice
  • Memory impairments
  • Mild traumatic brain injury
  • Opioid system

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