Reversible brain response to an intragastric load of l-lysine under l-lysine depletion in conscious rats

Abstract

l-Lysine (Lys) is an essential amino acid and plays an important role in anxiogenic behaviour in both human subjects and rodents. Previous studies have shown the existence of neural plasticity between the Lys-deficient state and the normal state. Lys deficiency causes an increase in noradrenaline release from the hypothalamus and serotonin release from the amygdala in rats. However, no studies have used functional MRI (fMRI) to compare the brain response to ingested Lys in normal, Lys-deficient and Lys-recovered states. Therefore, in the present study, using acclimation training, we performed fMRI on conscious rats to investigate the brain response to an intragastric load of Lys. The brain responses to intragastric administration of Lys (3 mmol/kg body weight) were investigated in six rats intermittently in three states: normal, Lys-deficient and recovered state. First, in the normal state, an intragastric load of Lys activated several brain regions, including the raphe pallidus nucleus, prelimbic cortex and the ventral/lateral orbital cortex. Then, after 6 d of Lys deprivation from the normal state, an intragastric load of Lys activated the ventral tegmental area, raphe pallidus nucleus and hippocampus, as well as several hypothalamic areas. After recovering from the Lys-deficient state, brain activation was similar to that in the normal state. These results indicate that neural plasticity in the prefrontal cortex, hypothalamic area and limbic system is related to the internal Lys state and that this plasticity could have important roles in the control of Lys intake.