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

Steady-state methadone blocks cocaine seeking and cocaine-induced gene expression alterations in the rat brain.
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DOI:
10.1016/j.euroneuro.2008.09.004
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发表时间:
2009-04
影响因子:
5.6
通讯作者:
Kreek, Mary Jeanne
Kreek, Mary Jeanne
中科院分区:
医学2区
文献类型:
--
作者:
Leri, Francesco;Zhou, Yan;Goddard, Benjamin;Levy, AnneMarie;Jacklin, Derek;Kreek, Mary Jeanne

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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.
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