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

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Abstract

Rationale

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

Objectives

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).

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

This study was supported by a grant for Interdisciplinary Project for Psychosomatological Research in Hokkaido University.

Conflicts of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Neuropharmacology, Graduate School of Medicine, Hokkaido University, N15 W7 Kita-ku, Sapporo, 060-8638, Japan

    Yu Ohmura, Iku Tsutsui-Kimura, Haruko Kumamoto, Takeshi Izumi, Taku Yamaguchi, Takayuki Yoshida & Mitsuhiro Yoshioka

  2. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12 W6 Kita-ku, Sapporo, 060-0812, Japan

    Masabumi Minami

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  1. Yu Ohmura
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Supplemental Fig. 1

The effects of lithium (a–f) on 3-CSRTT performance in rats whose amounts of food consumption were not affected by lithium (less than ±5%) administration. Based on the results of experiment 4 (Fig. 4), seven rats were selected from the data of experiment 5 (Fig. 5). Significant effects of 32 mg/kg of LiCl on premature responses were still observed (t = 4.81, p < 0.05), indicating that lithium has a suppressive effect on impulsive action independent of the anorexic effect. The bars represent the mean, and the lines represent the SEM. *p < 0.05 (PPT 136 kb)

Supplemental Fig. 2

The effects of lithium on responses during time-out in the 3-CSRTT. The combined data of experiments 1 and 5 were used for this figure. The bars represent the mean, and the lines represent the SEM (PPT 89 kb)

Supplemental Fig. 3

Scatter plot of the change rate of omissions and the change rate of food consumption by LiCl (32 mg/kg) administration. Each change rate was calculated by (performance at 32 mg/kg of LiCl/performance at vehicle − 1) × 100. No significant correlation was observed, indicating that the anorexic effects of LiCl are independent of the increasing effects of LiCl on omissions. Although it is speculated that an outlier might distort the correlation coefficient, even when we removed an outlier, the correlation was still no significant (r = −0.26, n = 16) (PPT 82 kb)

Supplemental Fig. 4

Scatter plot of the change rate of correct response latency and the change rate of food consumption by LiCl (32 mg/kg) administration. Each change rate was calculated by (performance at 32 mg/kg of LiCl/performance at vehicle − 1) × 100. No significant correlation was observed, indicating that the anorexic effects of LiCl are independent of the prolonging effects of LiCl on response latency (PPT 84 kb)

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Ohmura, Y., Tsutsui-Kimura, I., Kumamoto, H. et al. Lithium, but not valproic acid or carbamazepine, suppresses impulsive-like action in rats. Psychopharmacology 219, 421–432 (2012). https://doi.org/10.1007/s00213-011-2496-9

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