Perry Jennifer L, Morgan Andrew D, Anker Justin J, Dess Nancy K, Carroll Marilyn E
Department of Psychiatry, University of Minnesota Medical School, MMC 392, Minneapolis, MN 55455, USA.
Psychopharmacology (Berl). 2006 Jun;186(2):235-45. doi: 10.1007/s00213-006-0371-x. Epub 2006 Apr 5.
Rats selectively bred for high saccharin (HiS) intake consume more alcohol, acquire intravenous (i.v.) cocaine self-administration more rapidly, and show more dysregulated patterns of cocaine self-administration than their low saccharin-consuming (LoS) counterparts.
The purpose of the present study was to determine whether HiS and LoS rats also differ in the escalation, maintenance, extinction, and reinstatement of i.v. cocaine self-administration.
Two experiments were conducted in separate groups of rats. In the first experiment, HiS and LoS female rats were allowed to self-administer cocaine [0.4 mg/kg; fixed ratio (FR) 1] under short (ShA, 2 h per day) or long (LgA, 12 h per day) access conditions for 21 days. Session lengths were subsequently equated (2 h), and FR1-maintained cocaine self-administration was examined. In the second experiment, additional groups of HiS and LoS female rats were given access to cocaine (0.4 mg/kg; FR 1) self-administration during 2-h sessions for 10 days. Subsequently, saline was substituted for cocaine, and responding was extinguished. After a 14-day extinction period, saline- and cocaine-[5, 10, and 15 mg/kg, intraperitoneal (i.p.)] induced reinstatement of drug-seeking behavior was measured.
HiS LgA rats escalated their cocaine intake more rapidly than LoS rats, and during the 2 h sessions after escalation cocaine self-administration was significantly higher in HiS LgA rats, compared to LoS LgA rats. HiS rats responded on the cocaine-paired lever more than LoS rats during maintenance, extinction, and cocaine-(15 mg/kg) induced reinstatement.
These results suggest that HiS and LoS rats have distinct drug-seeking and drug-taking profiles. The HiS and LoS rats differ along a wide range of behavioral dimensions and represent an important model to study the interactions of excessive intake of dietary substances and vulnerability to drug abuse.
选择性培育出的高糖精（HiS）摄入大鼠比低糖精（LoS）摄入大鼠消耗更多酒精，更快习得静脉注射（i.v.）可卡因自我给药行为，且在可卡因自我给药模式上表现出更多失调情况。
本研究的目的是确定HiS和LoS大鼠在静脉注射可卡因自我给药的剂量递增、维持、消退和恢复方面是否也存在差异。
在不同组的大鼠中进行了两项实验。在第一个实验中，让HiS和LoS雌性大鼠在短（ShA，每天2小时）或长（LgA，每天12小时）给药条件下自我给药可卡因[0.4毫克/千克；固定比率（FR）1]，持续21天。随后使给药时长相等（2小时），并检查FR1维持的可卡因自我给药情况。在第二个实验中，额外的HiS和LoS雌性大鼠组在2小时的给药时段内进行可卡因（0.4毫克/千克；FR 1）自我给药，持续10天。随后，用生理盐水替代可卡因，使反应消退。在14天的消退期后测量生理盐水和可卡因-[5、10和15毫克/千克，腹腔内（i.p.）]诱导的觅药行为恢复情况。
HiS LgA大鼠比LoS大鼠更快增加可卡因摄入量，在剂量递增后的2小时给药时段内，HiS LgA大鼠的可卡因自我给药量显著高于LoS LgA大鼠。在维持、消退和可卡因-（15毫克/千克）诱导的恢复过程中，HiS大鼠在与可卡因配对的杠杆上的反应比LoS大鼠更多。
这些结果表明HiS和LoS大鼠具有不同的觅药和用药特征。HiS和LoS大鼠在广泛的行为维度上存在差异，是研究饮食物质过量摄入与药物滥用易感性相互作用的重要模型。
