Sub-anesthetic doses of ketamine produce an increase in rodent ambulation that is attenuated by co-administration of naturally-occurring lithium (LiN), the drug most commonly employed in the treatment of bipolar illness. As a consequence, ketamine-induced hyperactivity has been proposed as an animal model of manic behavior. The current study employed a modified version of this model to compare the potency of LiN to that of each of its two stable isotopes – lithium-6 (Li-6) and lithium-7 (Li-7). Since Li-7 constitutes 92.4% of the parent compound it was hypothesized to produce comparable behavioral effects to that of LiN. The current study was devised to determine whether Li-6 might be more, less, or equally effective at tempering hyperactivity relative to Li-7 or to LiN in an animal model of manic behavior. Male rats were maintained on a restricted but high-incentive diet containing a daily dose of 2.0 mEq/kg of lithium (LiN), Li-6 or Li-7 for 30 days. A control group consumed a diet infused with sodium chloride (NaCl) in place of lithium to control for the salty taste of the food. On day 30, baseline testing revealed no differences in the locomotor behavior among the four treatment groups. Animals then continued their Li/NaCl diets for an additional 11 days during which every subject received a single IP injection of either ketamine (25 mg/kg) or 0.9% physiological saline. On the final four days of this regimen, locomotor activity was assessed during 60 min sessions each beginning immediately after ketamine injection. While all three lithium groups produced comparable decreases in ketamine-induced hyperactivity on the first trial, by the fourth trial Li-6 animals exhibited significantly greater and more prolonged reductions in hyperactivity compared to either Li-7 and Li. These results suggest that Li-6 may be more effective at treating mania than its parent compound.

亚麻醉剂量的氯胺酮会增加啮齿动物的下肢活动，并与自然存在的锂（Li N）并用会减弱这种情况，锂是最常用于治疗躁郁症的药物。结果，已经提出了氯胺酮诱导的机能亢进作为躁狂行为的动物模型。当前的研究采用了该模型的改进版本，以比较Li N与其两种稳定同位素锂6（Li-6）和锂7（Li-7）的效力。由于Li-7占母体化合物的92.4％，因此可以假设产生与Li N相当的行为效果。本研究旨在确定Li-6相对于N-6而言在缓解多动性方面是否更有效，更有效或同等有效。 Li-7或Li躁狂行为动物模型中的N。雄性大鼠保持节制但高刺激性饮食，每天饮食中含有2.0 mEq / kg锂（LiN），Li-6或Li-7，持续30天。对照组在饮食中摄入了氯化钠（NaCl）代替锂，以控制食物的咸味。在第30天，基线测试显示四个治疗组之间的运动行为没有差异。然后，动物继续其Li / NaCl饮食另外11天，在此期间，每个受试者接受IP注射的氯胺酮（25mg / kg）或0.9％的生理盐水。在该方案的最后四天，在氯胺酮注射后立即开始的60分钟疗程中评估运动能力。虽然所有三个锂基团在首次试验中都产生了可观的氯胺酮诱导的过度活跃性下降，通过第四次试验，与Li-7和Li相比，Li-6动物表现出的过度活跃性显着更大，更长时间的降低。这些结果表明，Li-6可能比其母体化合物更有效地治疗躁狂症。