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  • Title: Combinations of oxazepam and metyrapone attenuate cocaine and methamphetamine cue reactivity.
    Author: Keller CM, Cornett EM, Guerin GF, Goeders NE.
    Journal: Drug Alcohol Depend; 2013 Dec 01; 133(2):405-12. PubMed ID: 23896309.
    Abstract:
    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.
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