在因糖精摄入量不同而选择性培育的大鼠中进行静脉注射可卡因和海洛因自我给药:表型和性别差异。
Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences.
作者信息
Carroll Marilyn E, Morgan Andrew D, Lynch Wendy J, Campbell Una C, Dess Nancy K
机构信息
Department of Psychiatry, University of Minnesota, Medical School, Box 392 Mayo, Minneapolis 55455, USA.
出版信息
Psychopharmacology (Berl). 2002 May;161(3):304-13. doi: 10.1007/s00213-002-1030-5. Epub 2002 Mar 27.
RATIONALE
Rats selectively bred for high intake of a sweet saccharin solution (HiS) consume more ethanol than their low-saccharin intake (LoS) counterparts. The HiS phenotype may be a predictor of abuse of other drugs via other routes of administration.
OBJECTIVE
HiS and LoS, male and female rats were tested for acquisition of IV cocaine and heroin self-administration under a fixed-ratio 1 (FR1) schedule, and cocaine-reinforced behavior was examined under a progressive-ratio (PR) schedule.
METHODS
Four groups of rats (HiS males and females and LoS males and females) were trained to self-administer IV cocaine (0.2 mg/kg), and another four groups were trained to self-administer heroin (0.015 mg/kg) using an automated autoshaping procedure. Rats were allowed 30 days to reach a criterion whereby a mean of 100 (cocaine) or 20 (heroin) infusions were self-administered during 6-h sessions over 5 consecutive days.
RESULTS
The HiS female rats acquired cocaine self-administration significantly more rapidly than the LoS rats, and females of both phenotypes met the acquisition criteria more rapidly than males. In both HiS and LoS cocaine groups a greater percentage of females (compared with males) met the acquisition criteria within 30 days. The only cocaine group in which 100% met the criterion was the HiS females. The female (compared with male) heroin groups showed a more rapid rate of acquisition, but there was no difference due to saccharin phenotype. In each of the four heroin groups 100% of all rats met the criteria within 30 days. Results of the PR schedule in the HiS females and males and LoS females indicated significantly higher break points in the HiS females (compared with HiS males), but there were no differences in females due to phenotype.
CONCLUSION
Female rats selectively bred for higher saccharin intake show more rapid and successful acquisition of IV self-administration of a low dose of cocaine than those bred for low saccharin intake. Female rats (compared with males) consistently showed accelerated rates of acquisition and maintenance (PR) of cocaine self-administration and acquisition of heroin self-administration.
原理
经选择性培育而成的对甜味糖精溶液高摄入量(HiS)的大鼠,比低糖精摄入量(LoS)的大鼠摄入更多乙醇。HiS表型可能是通过其他给药途径滥用其他药物的一个预测指标。
目的
对HiS和LoS的雄性和雌性大鼠进行测试,观察它们在固定比率1(FR1)模式下静脉注射可卡因和海洛因自我给药的习得情况,并在累进比率(PR)模式下检查可卡因强化行为。
方法
四组大鼠(HiS雄性和雌性以及LoS雄性和雌性)接受训练以自我静脉注射可卡因(0.2毫克/千克),另外四组大鼠使用自动塑造程序接受训练以自我静脉注射海洛因(0.015毫克/千克)。给予大鼠30天时间以达到一个标准,即连续5天在6小时的时段内平均自我注射100次(可卡因)或20次(海洛因)。
结果
HiS雌性大鼠比LoS大鼠更快地习得可卡因自我给药,并且两种表型的雌性大鼠比雄性大鼠更快地达到习得标准。在HiS和LoS可卡因组中,更大比例的雌性大鼠(与雄性相比)在30天内达到习得标准。唯一100%达到标准的可卡因组是HiS雌性大鼠组。雌性(与雄性相比)海洛因组显示出更快的习得速度,但因糖精表型没有差异。在四个海洛因组中的每组中,所有大鼠的100%在30天内达到标准。HiS雌性和雄性大鼠以及LoS雌性大鼠的PR模式结果表明,HiS雌性大鼠(与HiS雄性相比)的断点显著更高,但雌性大鼠因表型没有差异。
结论
经选择性培育而成的对糖精摄入量较高的雌性大鼠,比那些对糖精摄入量低的大鼠,在低剂量可卡因静脉自我给药的习得方面表现得更快且更成功。雌性大鼠(与雄性相比)始终显示出可卡因自我给药的习得和维持(PR)以及海洛因自我给药习得的加速速度。