Steady-state methadone blocks cocaine seeking and cocaine-induced gene expression alterations in the rat brain

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• 作者：Francesco Leri ; Yan Zhou ; Benjamin Goddard ; AnneMarie Levy ; Derek Jacklin ; Mary Jeanne Kreek
• 刊名：European Neuropsychopharmacology
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：19
• 期：4
• 页码：238-249
• 全文大小：1006 K

文摘

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.