Lithium/nutrition interaction in the brain: a single lithium administration impairs spreading depression in malnourished, but not in well-nourished rats.

Lithium salts exert electrophysiological and behavioral effects in animals and humans and have been used clinically in the treatment of bipolar disorders. Little is known about the lithium/nutrition interaction in the developing brain. This work aimed to determine, in adult rats, whether treatment with a single dose of lithium chloride (LiCl) would influence the propagation of the brain excitability-related phenomenon known as cortical spreading depression (CSD). Male well-nourished (W; fed a lab chow diet with 22% protein; n=22) and previously protein-malnourished rats (M; fed a low-quality 8% protein diet; proteins mostly from vegetable source; n=20) were treated at 75-80 days of age with a single intraperitoneal injection of either 50 mg/kg LiCl (n=9 W and 10 M rats) or saline (n=13 W and 10 M rats). When the pups were 90-110 days, CSD was elicited at the frontal cortex and recorded during 4 hours at two cortical parietal points. In malnourished, but not in well-nourished rats, lithium treatment lowered CSD velocities (P < 0.05), in comparison with saline-injected animals. In a third group (n=23), in which the low-protein diet was quantitatively corrected to 22%, the lithium effect disappeared (n=12), compared to saline (n=11). Our results demonstrate a facilitating effect of malnutrition on the CSD-impairing action of a single lithium administration, suggesting a lithium/nutrition interaction.