Enhancing effects of chronic lithium on memory in the rat

Background: In spite of recent enrichment of neurochemical and behavioural data establishing a neuroprotective role lot lithium, its primary effects on cognitive functioning remain ambiguous. This study examines chronic lithium effects on spatial working memory and long-term retention. Methods: In three discrete experiments, rats subjected to 30 daily intraperitoneal injections (2 mmol/kg) of lithium (lithium groups: serum lithium = 0.5 +/- 0.4 mEq/l, 12 h post-injection) or saline (controls) were trained in 0-s delay T-maze alternation and then tested in 30-, 45- and 60-s delay alternation (Experiments 1, 2, 3, respectively). Animals from Experiment 1 were further tested in one-trial step-through passive avoidance under mild shock parameters (0.5 mA, 1 s). Retention was assessed 6 h later. Daily lithium or saline injections continued throughout behavioural testing. Results: Lithium animals were indistinguishable from controls during 0-delay alternation baseline (Experiments 1-3. accuracy > 88%) but showed significantly higher accuracy than controls at 30- and 45-s delays (93% versus 85% and 92% versus 82%, Experiments 1 and 2, respectively). At 60-s delay (Experiment 3) this beneficial effect of lithium was no longer apparent (lithium and control accuracy = 78%). In Experiment 4, the shock used did not Support 6-h passive avoidance retention in controls, whereas lithium animals showed significant step-through latency increases. Conclusions: Chronic lithium enhanced spatial working memory and promoted long-term retention of a weak aversive contingency. The results suggest that lithium may have potential as a cognitive enhancer. (c) 2006 Elsevier B.V. All rights reserved.