Combinations of oxazepam and metyrapone attenuate cocaine and methamphetamine cue reactivity

Drug Alcohol Depend. 2013 Dec 1;133(2):405-12. doi: 10.1016/j.drugalcdep.2013.06.025. Epub 2013 Jul 26.


Background: We have previously reported that combining low doses of oxazepam and metyrapone (OX/MET) reduces intravenous cocaine self-administration without affecting stress-hormone levels. We hypothesized that the combination of OX/MET would also inhibit the reinstatement of cocaine or methamphetamine seeking induced by the presentation of a conditioned reinforcer and that stress hormone levels would not be influenced by this treatment.

Methods: Male rats were implanted with jugular catheters and trained to self-administer cocaine or methamphetamine during daily 2-h sessions. During training, cocaine or methamphetamine delivery was paired with the presentation of a tone and the illumination of a house light. Following stable self-administration, rats were placed into forced abstinence. During cue-reactivity testing, rats were placed back into the operant chambers and responding only resulted in the presentation of the conditioned reinforcer; no cocaine or methamphetamine was delivered. Blood was collected on the last day of self-administration and on the day of cue-reactivity testing (either 15-min or 2-h session) to assess plasma corticosterone.

Results: The response-contingent presentation of the conditioned reinforcer reliably maintained cocaine or methamphetamine seeking following vehicle pretreatment. Pretreatment with OX/MET resulted in a dose-related attenuation of both cocaine and methamphetamine seeking. Corticosterone levels were significantly different at the end of the 15-min session, but not following the 2-h session.

Conclusion: These data suggest that OX/MET may be useful in blocking the ability of environmental cues to stimulate both cocaine and methamphetamine seeking and that this effect is not entirely dependent on stress hormone levels.

Keywords: Cocaine; Corticosterone; Cue reactivity; Methamphetamine; Metyrapone; Oxazepam.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine-Related Disorders / psychology*
  • Analysis of Variance
  • Animals
  • Central Nervous System Stimulants*
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Corticosterone / antagonists & inhibitors
  • Corticosterone / biosynthesis
  • Corticosterone / blood
  • Cues
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Food
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Methamphetamine*
  • Metyrapone / pharmacology*
  • Oxazepam / pharmacology*
  • Pharmaceutical Vehicles
  • Rats
  • Rats, Wistar
  • Self Administration
  • Substance Withdrawal Syndrome / psychology


  • Central Nervous System Stimulants
  • Enzyme Inhibitors
  • Hypnotics and Sedatives
  • Pharmaceutical Vehicles
  • Methamphetamine
  • Oxazepam
  • Corticosterone
  • Metyrapone