Anxiogenic-like effects of spontaneous and naloxone-precipitated opiate withdrawal in the elevated plus-maze.
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.
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Schulteis
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Yackey
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Risbrough
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Koob
D000818:Animals; D001007:Anxiety / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine