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Effects of Combinations of Metyrapone and Oxazepam on Methamphetamine Cue Reactivity and the HPA Axis in Rats
Author(s) -
Miller Andrew Joseph,
Cornett Elyse,
Guerin Glenn,
Goeders Nick
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1040.8
Subject(s) - meth , craving , methamphetamine , metyrapone , cue reactivity , addiction , psychology , corticosterone , oxazepam , self administration , abstinence , amphetamine , pharmacology , medicine , endocrinology , benzodiazepine , chemistry , hormone , neuroscience , psychiatry , dopamine , receptor , monomer , organic chemistry , acrylate , polymer
METH is a highly addictive psychostimulant. There is currently no FDA approved treatment for METH addiction. Study in our lab focuses on the role of the stress response and the influence of environmental cues in accounting for the high rate of relapse in recovering addicts (60% relapse for METH patients). The combination of Metyrapone (MET, a CORT synthesis inhibitor) and Oxazepam (OX, a benzodiazepine) has been shown to decrease both cocaine self‐administration and cue‐induced reinstatement. The MET/OX combination was used in these experiments to test its effects on cue‐induced METH craving in rats. Rats were trained to self‐administer METH via lever response. Drug delivery was paired with a tone and the illumination of a houselight, both serving as secondary reinforcers, or cues. After stable self‐administration of METH for at least 10 days, subjects entered a 2‐week abstinence period. Rats were then given a cue reactivity test wherein the cues were presented at lever response, but no METH was delivered. With vehicle pretreatment, the response‐contingent presentation of the cues reliably maintained METH seeking (i.e. lever responses). Pretreatment with the MET/OX combination attenuated responding at both doses tested, suggesting diminished craving. Levels of stress hormones corticosterone (CORT) and ACTH were measured to ensure that the MET/OX combination did not cause adrenal insufficiency.