Witkin J M, Goldberg S R
Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Pharmacol Biochem Behav. 1990 Oct;37(2):339-42. doi: 10.1016/0091-3057(90)90345-i.
Effects of cocaine on several behaviors considered to be reflective of psychomotor stimulation were compared in F344/CR1BR and NBR/NIH inbred rat strains. Effects of cocaine on locomotor activity were compared with effects on either bar-press or nose-poke responses maintained under a multiple fixed-interval 3-min, timeout 1-min schedule of food presentation. In locomotor activity experiments, NBR rats were twice as active as F344 rats under baseline conditions and displayed dose-dependent increases in locomotion (5-20 mg/kg). Maximal increases in locomotor activity of F344 rats were only 200% compared to 1000% in NBR rats. In contrast to locomotor activity, no strain differences in the effects of cocaine were observed under the schedules of food delivery. Bar-pressing under the fixed-interval schedule was increased to a maximum of 150% of control in both rat strains. Nose-poke responding under the fixed-interval schedule was not significantly increased, but timeout rates were increased in both strains. These results suggest that NBR and F344 rats do not differ in general sensitivity to stimulant effects of cocaine but exhibit marked differences in responsivity to cocaine that are dependent upon the behavior studied. Further delineation of the behavioral specificity of strain differences in sensitivity to cocaine should help to identify neurobiological substrates underlying unique biologically determined responses to cocaine.
在F344/CR1BR和NBR/NIH近交系大鼠品系中,比较了可卡因对几种被认为反映精神运动性兴奋的行为的影响。将可卡因对运动活动的影响与对在多重固定间隔3分钟、超时1分钟的食物呈现时间表下维持的压杆或鼻触反应的影响进行了比较。在运动活动实验中,在基线条件下,NBR大鼠的活动量是F344大鼠的两倍,并且在运动方面表现出剂量依赖性增加(5-20毫克/千克)。F344大鼠运动活动的最大增加仅为200%,而NBR大鼠为1000%。与运动活动相反,在食物递送时间表下未观察到可卡因作用的品系差异。在固定间隔时间表下压杆在两种大鼠品系中均增加到对照的最大150%。在固定间隔时间表下鼻触反应没有显著增加,但两种品系的超时率均增加。这些结果表明,NBR和F344大鼠对可卡因的兴奋作用的总体敏感性没有差异,但对可卡因的反应性表现出明显差异,这取决于所研究的行为。进一步阐明品系对可卡因敏感性差异的行为特异性,应有助于确定对可卡因独特的生物学决定反应的神经生物学基础。