Sudakov S K, Goldberg S R, Borisova E V, Surkova L A, Turina I V, Elmer G I
Laboratory of Experimental Therapy of Drug Abuse, All-Union Research Center of Addictions, Moscow, Russia.
Psychopharmacology (Berl). 1993;112(2-3):183-8. doi: 10.1007/BF02244908.
The purpose of the current study was to investigate genetic differences between two inbred strains of rats, Fisher-344 (F344/N) and Wistar Albino Glaxo (WAG/GSto), in a number of drug-naive and drug-related behaviors, including oral and intravenous morphine self-administration. F344/N and WAG/GSto rats differed in drug-naive behaviors such as nociception, rearing and sensitivity to lick suppression tests but did not differ in locomotor activity, ambulation or grooming behavior. F344/N rats were less sensitive to thermal stimuli as measured via tail-flick response, and more sensitive to the suppressive effects of intermittent shock in a lick suppression test. The F344/N rats demonstrated a significantly greater amount of rearing in open field tests but did not differ from WAG/GSto rats in locomotor activity, ambulation or grooming behavior. In addition to the behavioral results, naive F344/N and WAG/GSto rats were found to differ in mu and alpha 2 receptor concentrations (F344/N > WAG/GSto) and in 5HT2 and D2 affinity constants (WAG/GSto > F344/N). These two inbred rat strains also differed in drug-related behaviors. F344/N rats showed significantly greater depression of locomotor activity at morphine 3 mg/kg than WAG/GSto rats. In addition, F344/N rats consumed significantly greater amounts of morphine in a two-bottle choice procedure and morphine maintained significantly greater amounts of behavior during intravenous self-administration sessions. Importantly, drug maintained behavior was significantly greater than with vehicle only in the F344/N rats during operant self-administration sessions.
本研究的目的是调查两种近交系大鼠,即费希尔-344(F344/N)和威斯塔白化葛兰素(WAG/GSto),在多种未接触过药物及与药物相关行为方面的基因差异,包括口服和静脉注射吗啡自我给药。F344/N和WAG/GSto大鼠在未接触过药物的行为上存在差异,如伤害感受、竖毛和对舔舐抑制试验的敏感性,但在运动活动、行走或梳理行为方面没有差异。通过甩尾反应测量,F344/N大鼠对热刺激的敏感性较低,而在舔舐抑制试验中对间歇性电击的抑制作用更敏感。在旷场试验中,F344/N大鼠表现出显著更多的竖毛行为,但在运动活动、行走或梳理行为方面与WAG/GSto大鼠没有差异。除行为结果外,还发现未接触过药物的F344/N和WAG/GSto大鼠在μ和α2受体浓度(F344/N > WAG/GSto)以及5HT2和D2亲和力常数(WAG/GSto > F344/N)方面存在差异。这两种近交系大鼠在与药物相关的行为上也存在差异。在注射3mg/kg吗啡时,F344/N大鼠的运动活动抑制程度明显高于WAG/GSto大鼠。此外,在双瓶选择程序中,F344/N大鼠消耗的吗啡量显著更多,并且在静脉自我给药期间,吗啡维持的行为量显著更多。重要的是,在操作性自我给药期间,仅在F344/N大鼠中,药物维持的行为明显大于使用溶剂时的行为。