Abstract
To elucidate the effects of steady-state methadone exposure on responding to cocaine conditioned stimuli and on cocaine-induced alterations in central opioid, hypocretin/orexin, and D2 receptor systems, male Sprague-Dawley rats received intravenous infusions of 1 mg/kg/inf cocaine paired with an audiovisual stimulus over three days of conditioning. Then, mini pumps releasing vehicle or 30 mg/kg/day methadone were implanted (SC), and lever pressing for the stimulus was assessed in the absence of cocaine and after a cocaine prime (20 mg/kg, IP). It was found that rats treated with vehicle, but not methadone, responded for the cocaine conditioned stimulus and displayed elevated mu-opioid receptor mRNA expression in the nucleus accumbens core and basolateral amygdala, reduced hypocretin/orexin mRNA in the lateral hypothalamus, and reduced D2 receptor mRNA in the caudate-putamen. This is the first demonstration that steady-state methadone administered after cocaine exposure blocks cocaine-induced behavioral and neural adaptations.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acoustic Stimulation / methods
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Analgesics, Opioid / administration & dosage*
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Analysis of Variance
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Animals
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Behavior, Animal / drug effects
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Brain / drug effects*
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Cocaine / pharmacology*
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Cocaine-Related Disorders / drug therapy
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Cocaine-Related Disorders / metabolism
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Conditioning, Classical / drug effects
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Conditioning, Operant / drug effects
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Dopamine Uptake Inhibitors / pharmacology*
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Drug Administration Schedule
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Drug Delivery Systems / methods
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Dynorphins / genetics
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Dynorphins / metabolism
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Gene Expression Regulation / drug effects*
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Locomotion / drug effects
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Male
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Methadone / administration & dosage*
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Neuropeptides / genetics
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Neuropeptides / metabolism
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Orexins
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Photic Stimulation / methods
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Dopamine D2 / genetics
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Receptors, Dopamine D2 / metabolism
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Receptors, Opioid, mu / genetics
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Receptors, Opioid, mu / metabolism
Substances
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Analgesics, Opioid
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Dopamine Uptake Inhibitors
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Intracellular Signaling Peptides and Proteins
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Neuropeptides
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Orexins
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RNA, Messenger
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Receptors, Dopamine D2
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Receptors, Opioid, mu
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Dynorphins
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Cocaine
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Methadone