Differential effects of lithium isotopes in a ketamine-induced hyperactivity model of mania

Publication date: Available online 19 February 2020Source: Pharmacology Biochemistry and BehaviorAuthor(s): Aaron Ettenberg, Kathy Ayala, Jacob T. Krug, Lisette Collins, Matthew S. Mayes, Matthew P.A. FisherAbstractSub-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 of the treatment groups. Animals then continued their Li/NaCl diets for an additional 1...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research