Ketoconazole reduces low dose cocaine self-administration in rats
Ketoconazole reduces low dose cocaine self-administration in rats
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DOI：
10.1016/s0376-8716(98)00108-2
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发表时间：
1998-12-01
影响因子：
4.2
通讯作者：
Guerin, GF
中科院分区：
文献类型：
--
作者：
Goeders, NE;Peltier, RL;Guerin, GF
酮康唑是FDA批准的用于治疗真菌疾病的口服抗真菌药，其还阻断肾上腺皮质类固醇的合成并作为糖皮质激素受体拮抗剂发挥作用。在这些实验中，允许成年雄性Wistar大鼠在每天2小时的会议期间交替15分钟的食物强化和可卡因自我给药（每次输注0.125，0.25或0.5 mg/kg）。一个I-min超时分隔了对两个缓存器的访问。用酮康唑（25 mg/kg，i. p.）显著降低血浆皮质酮和减少低剂量（即0.125-0.25 mg/kg/输注）可卡因自我给药，而不影响食物强化反应。事实上，酮康唑预处理导致这些剂量下的自我给药率和模式与可卡因消退期间观察到的情况无法区分。然而，在这些实验中测试的最高剂量（即每次输注0.5 mg/kg）下的可卡因自我给药未受到酮康唑的显著影响。这些数据表明，酮康唑或相关药物在治疗可卡因滥用中作为镇静剂的潜在效用，并进一步强调了皮质酮在可卡因强化中的作用。(C)1998爱思唯尔科学爱尔兰有限公司保留所有权利。
Ketoconazole is an oral antimycotic agent approved by the FDA for the treatment of fungal disease which also blocks the synthesis of adrenocorticosteroids and functions as a glucocorticoid receptor antagonist. In these experiments, adult male Wistar rats were allowed alternating 15-min periods of access to food reinforcement and cocaine self-administration (0.125, 0.25 or 0.5 mg/kg per infusion) during daily 2-h sessions. A I-min timeout separated access to the two reinforcers. Pretreatment with ketoconazole (25 mg/kg, i.p.) significantly decreased plasma corticosterone and reduced low dose (i.e. 0.125-0.25 mg/kg per infusion) cocaine self-administration without affecting food-reinforced responding. In fact, pretreatment with ketoconazole resulted in rates and patterns of self-administration at these doses that were indistinguishable from those observed during cocaine extinction. However, cocaine self-administration at the highest dose tested in these experiments (i.e. 0.5 mg/kg per infusion) was not significantly affected by ketoconazole. These data suggest the potential utility of ketoconazole or related drugs as adjuncts in the treatment of cocaine abuse and further underscore the role for corticosterone in cocaine reinforcement. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.