Lithium, but not valproic acid or carbamazepine, suppresses impulsive-like action in rats

Higher impulsivity is a pathological symptom in several psychiatric disorders, including bipolar disorder, and is a risk factor for suicide.

Our goal was to determine whether major mood-stabilizing drugs used for the treatment of bipolar disorder could suppress impulsive-like action in the three-choice serial reaction time task (3-CSRTT).

Following training for the 3-CSRTT, rats were acutely administered lithium chloride (LiCl; 0, 3.2, 10, and 32 mg/kg, i.p.), valproic acid (0, 10, 32, and 100 mg/kg, i.p.), or carbamazepine (0, 10, 20, and 30 mg/kg, i.p.). To assess the anorexic effects of lithium, a simple food consumption test was conducted.

LiCl dose-dependently decreased the number of premature responses, an index of impulsive-like action. A high dose of LiCl (32 mg/kg) decreased food consumption, but its anorexic effects were not correlated with the effects of LiCl on premature responses. A moderate dose of LiCl (20 mg/kg) significantly reduced the number of premature responses without affecting motivation-related measures in the 3-CSRTT or the amount of food consumption. Although carbamazepine prolonged reward latency, an index of motivation for food, neither valproic acid nor carbamazepine significantly affected premature responses.

It is likely that lithium has a suppressive effect on impulsive action independent of the anorexic effect. Lithium may suppress impulsive behavior and thereby decrease the risk of suicide. The present results could provide an explanation for the antisuicidal effects of lithium and suggest that lithium could be a beneficial treatment for impulsivity-related disorders.