Baclofen has opposite effects on escalation of cocaine self-administration: Increased intake in rats selectively bred for high (HiS) saccharin intake and decreased intake in those selected for low (LoS) saccharin intake
Baclofen has opposite effects on escalation of cocaine self-administration: Increased intake in rats selectively bred for high (HiS) saccharin intake and decreased intake in those selected for low (LoS) saccharin intake
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DOI：
10.1016/j.pbb.2011.08.028
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发表时间：
2011-12-01
影响因子：
3.6
通讯作者：
Carroll, Marilyn E.
中科院分区：
文献类型：
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作者：
Holtz, Nathan A.;Carroll, Marilyn E.
选择性饲养的高糖精摄入量（HiS）的大鼠自我管理更多的可卡因，在长期访问期间增加可卡因摄入量，并恢复可卡因寻求比低糖精摄入量（LoS）饲养的更高水平。本研究旨在确定巴氯芬（GABA（B）受体激动剂）是否对HIS和LoS大鼠静脉注射可卡因摄入量的增加和可卡因寻求的恢复具有不同的影响。HiS和LoS大鼠在每天2小时的短期访问（ShA）阶段自我施用可卡因3天，然后长期访问（LGA）会话21天，然后是第二个ShA阶段。一组HiS和LoS大鼠接受2.5 mg/kg巴氯芬（分别为HIS + B和LoS + B）的腹膜内注射，其他组HiS和LoS大鼠在每日疗程前接受生理盐水（HiS + Sal和LoS + Sal）。在第二个实验中。HiS和LoS大鼠在14天的2小时会议期间自我静脉注射可卡因，然后是21天的灭绝期。巴氯芬（2.5mg/kg，i. p.）或生理盐水在生理盐水或可卡因引发的恢复期之前施用。HiS + B组增加了可卡因自我给药，并在LgA ShA后阶段增加了可卡因输注。与LoS + Sal或HiS组相比，LoS + B组在整个LgA期间自我施用的可卡因较少。巴氯芬减弱了HiS和LoS大鼠可卡因寻求的恢复，没有表型差异。因此，巴氯芬在升级过程中对HiS和LoS大鼠的可卡因摄入量有相反的影响，但在恢复过程中有相似的影响。这些结果表明，治疗效果可能因个体差异（HiS与LoS）和建模的药物动机行为阶段而异。爱思唯尔公司出版
Rats selectively bred for high saccharin intake (HiS) self-administer more cocaine, escalate their cocaine intake during long access, and reinstate cocaine seeking at higher levels than those bred for low saccharin intake (LoS). The present study was conducted to determine if baclofen, an agonist at the GABA(b) receptor, has differential effects on the escalation of i.v. cocaine intake and reinstatement of cocaine-seeking in HIS and LoS rats. HiS and LoS rats self-administered cocaine during a 2-h daily short-access (ShA) phase for 3 days and then long-access (LgA) sessions for 21 days followed by a second ShA phase. One group of HiS and LoS rats received i.p. injections of 2.5 mg/kg baclofen (HIS + B and LoS + B, respectively), and other groups of HiS and LoS rats received saline (HiS + Sal and LoS + Sal) before each daily session. In a second experiment. HiS and LoS rats self-administered i.v. cocaine during 2-h sessions for 14 days followed by a 21-day extinction period. Baclofen (2.5 mg/kg, i.p.) or saline was administered before saline- or cocaine-primed reinstatement sessions. The HiS + B group escalated their cocaine self-administration and had increased cocaine infusions in the post-LgA ShA phase. The LoS + B group self-administered less cocaine throughout the entire LgA period compared to the LoS + Sal or HiS groups. Baclofen attenuated reinstatement of cocaine seeking in both the HiS and LoS rats with no phenotype differences. Thus, baclofen had opposite effects on cocaine intake in HiS and LoS rats during escalation; but similar effects during reinstatement. These results suggest that treatment effects might vary with individual differences (HiS vs. LoS) and the phase of drug-motivated behavior that is modeled. Published by Elsevier Inc.