Chronic lithium treatment magnifies learning in rats.

Recent electrophysiological work shows that chronic lithium treatment increases long-term potentiation (LTP) in neurons of the hippocampus, and LTP is thought to be the major neurophysiological basis for the development of learning and memory. This suggests that lithium might enhance learning and memory. Available studies have mainly assessed memory using aversive conditioning paradigms, but very little is available on the effect of lithium on learning. Since lithium may diminish anxiety or negative affect in adult rats, which would hinder aversive learning, the present study used three different positive reinforcement spatial cognitive tasks to determine whether chronic lithium affects learning. Each task differed in complexity, in the type of learning required, and in the reward received. For 4 weeks prior to, and throughout all learning assessments, rats had continual access to lithium chow or to a control chow diet. After 4 weeks' access to their designated chow diet, rats began conditioning in the hole-board spatial discrimination or T-maze delayed alternation tasks in a counterbalanced fashion. They immediately began conditioning in the opposite task once completing the first. This was then followed with social place-preference conditioning, after 24-h isolation from their home-cage social partner. Chronic lithium increased learning in all three paradigms, regardless of the reward received. Indeed, both food and social interaction supported enhanced learning. Thus the learning effect was not merely due to an effect of lithium on food palatability. Importantly, clinically relevant serum lithium levels were evidenced at the time of testing. Lithium also marginally enhanced memory as well. Thus chronic lithium treatment may improve learning and memory in Alzheimer's disease, and do so not only by blocking the formation of beta-amyloid and neurofibrillary tangles as suggested by previous research, but also by enhancing mechanisms involved in basal learning and memory formation, such as hippocampal synaptic plasticity.