Psychopharmacology

, Volume 181, Issue 3, pp 576–581 | Cite as

Ultra-low-dose naltrexone suppresses rewarding effects of opiates and aversive effects of opiate withdrawal in rats

Original Investigation

Abstract

Rationale

Ultra-low-dose opioid antagonists enhance opiate analgesia and attenuate tolerance and withdrawal.

Objectives

To determine whether ultra-low-dose naltrexone (NTX) coadministration alters the rewarding effects of opiates or the aversive effects of opiate withdrawal.

Methods

We used the conditioned place preference (CPP) and conditioned place aversion (CPA) paradigms to assess whether ultra-low-dose NTX alters the acute rewarding effects of oxycodone or morphine, or the aversive aspect of withdrawal from either drug. To assess the dose response for ultra-low-dose NTX, a range of NTX doses (0.03–30 ng/kg) was tested in the oxycodone CPP experiment. In order to avoid tolerance or sensitization effects, we used single conditioning sessions and female rats, as females are more sensitive to the conditioning effects of these drugs.

Results

Ultra-low-dose NTX (5 ng/kg) blocked the CPP to morphine (5 mg/kg) and the CPA to withdrawal from chronic morphine (5 mg/kg, for 7 days). Coadministration of ultra-low-dose NTX (30 pg/kg) also blocked the CPA to withdrawal from chronic oxycodone administration (3 mg/kg, for 7 days). The effects of NTX on the CPP to oxycodone (3 mg/kg) revealed a biphasic dose response. The two lowest doses (0.03 and 0.3 ng/kg) blocked the CPP, the middle dose (3 ng/kg) was ineffective, and oxycodone combined with the highest dose (30 ng/kg) produced a trend toward a CPP.

Conclusions

Ultra-low-dose NTX coadministration blocks the acute rewarding effects of analgesic doses of oxycodone or morphine as well as the anhedonia of withdrawal from chronic administration.

Keywords

Withdrawal Reward Oxycodone Morphine Naltrexone Place preference Place aversion 

Notes

Acknowledgements

The technical assistance of Jay Paquette and Stephanie Hancock is gratefully acknowledged. This work was funded by Pain Therapeutics, Inc.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of PsychologyQueen's UniversityKingstonCanada
  2. 2.Pain Therapeutics, Inc.South San FranciscoUSA

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