Anxiogenic-like effects of spontaneous and naloxone-precipitated opiate withdrawal in the elevated plus-maze

Pharmacol Biochem Behav. 1998 Jul;60(3):727-31. doi: 10.1016/s0091-3057(98)00034-3.

Abstract

Withdrawal from opiates and other drugs of abuse in human addicts is associated with a state of anxiety that may be of motivational relevance for the maintenance of drug addiction. Previous attempts with rats to model the anxiogenic-like effects of opiate withdrawal using the elevated plus-maze have met with mixed success. The current study sought to determine whether spontaneous and naloxone-precipitated opiate withdrawal could be observed reliably in rats made dependent on morphine through implantation of two morphine pellets (75 mg morphine base each). Seventy-two hours after implantation of either morphine or placebo pellets, rats were tested in the elevated plus-maze. In Experiment 1, pellets were removed 8 or 12 h prior to test; results indicated an anxiogenic-like effect (reduction in time spent in the open arms) of opiate withdrawal at 8 but not 12 h postpellet removal. In Experiment 2, pellets were not removed, but withdrawal was precipitated with naloxone (0.003-0.03 mg/kg s.c.). Naloxone dose dependently precipitated a reduction in exploration of the open arms of the plus-maze. The results suggest that both spontaneous and precipitated withdrawal from continuous morphine administration via pellet implantation result in demonstrable anxiogenic-like effects in the plus-maze.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anxiety / psychology*
  • Dose-Response Relationship, Drug
  • Male
  • Morphine / adverse effects*
  • Naloxone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Narcotics / adverse effects*
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome / psychology*

Substances

  • Narcotic Antagonists
  • Narcotics
  • Naloxone
  • Morphine