title: Increased elevated plus maze open-arm time in mice during naloxone-precipitated morphine withdrawal.
abstract: Opioid withdrawal is known to be anxiogenic in humans and, using the elevated plus maze (EPM), was demonstrated to also be anxiogenic in rats. Thus, this study characterizes EPM behaviors of mice during naloxone-precipitated morphine withdrawal. Naloxone did not significantly change EPM behaviors of drug-naïve mice. Additionally, morphine-dependent mice in which withdrawal was not precipitated (i.e. morphine-dependent mice receiving saline) spent less time in the open-arms compared to the controls. Surprisingly, increased open-arm time was observed in morphine-dependent mice undergoing naloxone-precipitated withdrawal. This increase was not because of total motor activity, as no significant differences in total activity were observed. Moreover, morphine dependency was necessary, given that there was not a significant increase in open-arm time for mice undergoing withdrawal from acute morphine. Increased open-arm time during withdrawal is unexpected, given that opioid withdrawal is usually associated with anxiety. Additionally, even in mice, naloxone-precipitated morphine withdrawal is known be aversive and increases plasma corticosterone levels. In conclusion, this study demonstrates somewhat unexpected EPM behavior in mice undergoing naloxone-precipitated morphine withdrawal. Possible interpretations of these EPM results, though somewhat speculative, raise the possibility that EPM behaviors might not be driven exclusively by anxiety levels but rather by other withdrawal-induced behaviors.
authors.affiliation: Behavioral and Cellular Neuroscience, Department of Psychology, Texas A & M University, College Station, Texas 77843, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Hodgson
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Hofford
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Norris
authors.forename: Shoshana
authors.initials: S
authors.lastname: Eitan
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009294:Narcotics / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine; D003345:Corticosterone