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Dopamine mediates cocaine-induced conditioned taste aversions as demonstrated with cross-drug preexposure to GBR 12909

机译:多巴胺介导可卡因诱导的条件性味觉厌恶,如交叉药物预暴露于GBR 12909所示

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摘要

Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. It has been suggested that its inhibitory effects at one of the monoamine transporters may be mediating this suppression. Using the cross-drug preexposure preparation, the present series of studies examined a possible role of dopamine (DA) in this effect. Male Sprague-Dawley rats were exposed to cocaine (18 mg/kg; Experiment 1) or the selective DA transporter (DAT) inhibitor GBR 12909 (50 mg/kg; Experiment 2) prior to the pairing of a novel saccharin solution with injections of GBR 12909 (32 mg/kg), cocaine (18 mg/kg) or vehicle in a conditioned taste aversion (CTA) procedure. Preexposure to cocaine attenuated aversions induced by itself but not aversions induced by GBR 12909 (Experiment 1). Conversely, preexposure to GBR 12909 attenuated aversions induced by itself and cocaine (Experiment 2). This asymmetry suggests that cocaine and GBR 12909 induce CTAs via similar, but non-identical, mechanisms. These data are discussed in the context of previous work demonstrating roles for dopamine, norepinephrine and serotonin in cocaine-induced CTAs.
机译:尽管可卡因很容易引起口感厌恶,但对该作用的潜在机制了解甚少。已经提出,其对单胺转运蛋白之一的抑制作用可能在介导这种抑制作用。使用交叉药物预暴露制剂,本系列研究研究了多巴胺(DA)在这种作用中的可能作用。将雄性Sprague-Dawley大鼠与可卡因(18 mg / kg;实验1)或选择性DA转运蛋白(DAT)抑制剂GBR 12909(50 mg / kg;实验2)接触,然后将新的糖精溶液与下列药物配对GBR 12909(32 mg / kg),可卡因(18 mg / kg)或赋形剂采用条件性味觉厌恶(CTA)程序进行。预先暴露于可卡因可减轻由其自身引起的厌恶,但不能减弱由GBR 12909引起的厌恶(实验1)。相反,对GBR 12909的预暴露可减轻其自身和可卡因引起的厌恶感(实验2)。这种不对称性表明可卡因和GBR 12909通过相似但不相同的机制诱导CTAs。在先前的工作中讨论了这些数据,这些工作证明了多巴胺,去甲肾上腺素和5-羟色胺在可卡因诱导的CTAs中的作用。

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