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 for 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 (2mmol/kg) of lithium (lithium groups: serum lithium=0.5+/-0.4mEq/l, 12h 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 (0.5mA, 1s). Retention was assessed 6h 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.
Tsaltas
Eleftheria
E
Athens University Medical School, Department of Psychiatry, Experimental Psychology Laboratory, Eginition Hospital, 74, Vas. Sofias Avenue, 115 28 Athens, Greece. tsaltasl@med.uoa.gr
Kontis
Dimitrios
D
Boulougouris
Vasileios
V
Papakosta
Vasiliki-Maria
VM
Giannou
Haralambos
H
Poulopoulou
Cornelia
C
Soldatos
Constantine
C
D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal; D004334:Drug Administration Schedule; D018021:Lithium Chloride / Q000008:administration & dosage* / Q000097:blood; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012201:Reward; D013997:Time Factors
D018692:Antimanic Agents; D018021:Lithium Chloride