Analyzing Turning Behavior after Repeated Lithium, Ketamine, or NaCl Injection and Chronic Stress Exposure in Mice

Abstract

A single chronic stress is often considered a potential reinforcer in psychiatric disorders. Lithium and ketamine both seem to ameliorate the consequences of stress. Here, male mice were either injected with lithium carbonate (LiCl), ketamine hydrochloride (KET), or sodium chloride (NaCl; controls) over nine consecutive days. Treatment was followed by 2 h of restraint stress over the first seven days. On the 9th day, 2 h after injection, all animals were tested in the open field, and novel object tests and behavior were analyzed using the toolbox ‘DeepLabCut’. To exclude an effect of generally altered locomotion activity on turning behavior, further parameters were assessed. Treatment before chronic stress exposure did not influence the total number of turns, nor the direction of turning behavior in the open field and the novel object test. Additionally, general locomotion did not differ. However, mice treated with LiCl showed a stronger turning bias (i.e., larger absolute lateralization quotients) in the novel object test when compared to mice treated with KET. This study underlines the potential of investigating turning behavior as a sensitive and reliable marker of stress reaction. Additionally, analyzing behavioral asymmetries in the context of psychopharmacological treatment can render new insights.