Acute administration of lithium, but not valproate, modulates cognitive judgment bias in rats.

Rafal Rygula,Joanna Golebiowska,Malgorzata Holuj,Piotr Popik,Jakub Kregiel

doi:10.1007/s00213-014-3847-0

Abstract

Rationale and objectivesBoth valproic acid (VPA) and lithium (LI) are well-established treatments for therapy of intense and sustained mood shifts, which are characteristics of affective disorders, such as bipolar disorder (BP). As mood and cognitive judgment bias have been found to be strongly interrelated, the present study investigated, in an animal model, whether acute treatment with VPA or LI could affect cognitive judgment bias.MethodsTo accomplish this goal, two groups of rats received single injections of either VPA or LI after initial behavioral training and were subsequently tested with the ambiguous-cue interpretation (ACI) test. Both drugs were administered in three doses using the fully randomized Latin square design.ResultsVPA (100, 200, and 400 mg/kg) had no significant effect on the interpretation of the ambiguous cue. LI at the lowest dose (10 mg/kg) had no effect; at an intermediate dose (50 mg/kg), it significantly biased animals towards positive interpretation of the ambiguous cue, and at the highest dose (100 mg/kg), it impaired the ability of animals to complete the test.ConclusionTo our knowledge, this is the first study demonstrating lithium’s effects on increased optimistic judgment bias. Future studies may focus on the ability of putative pharmacotherapies to modify the cognitive judgment bias dimension of patients at risk for bipolar disorder or depression.

Highlights

Over 60 years have elapsed since its effects on mania were first described, lithium (LI) is still a mainstay in the treatment of mood disorders and remains the standard against which new mood-stabilizing or thymoleptic drugs are measured (Price and Heninger 1994)
The animals that were used in the experiment with LI reached the criteria of positive tone, negative tone, and discrimination trainings after 5.6±0.38, 7.9±1.3, and 28.8± 1.0 days, respectively, whereas the group used in the experiment with valproic acid (VPA) reached the criteria after 5.2±0.3, 20.1±1.7, and 30.1±2.1 days, respectively
In the present study, using the recently developed ambiguouscue interpretation test, we investigated whether acute treatment with LI or VPA could affect cognitive judgment bias in an animal model

Summary

Introduction

Over 60 years have elapsed since its effects on mania were first described, lithium (LI) is still a mainstay in the treatment of mood disorders and remains the standard against which new mood-stabilizing or thymoleptic drugs are measured (Price and Heninger 1994). The mechanism by which LI effectively treats bipolar disorder (BP) and depression and reduces the risk of suicidal behaviors is largely unknown. Another well-established treatment for bipolar disorder is valproic acid (VPA). The drug is increasingly used for therapy of bipolar and schizoaffective disorders and neuropathic pain and for prophylactic treatment of migraines (Johannessen 2000; Johannessen and Johannessen 2003); similar to LI, its mode of action, especially on the systems level, remains unknown. Important insights regarding the mechanism of action of these drugs may arise from understanding the effects of LI and VPA on cognitive biases associated with affective disorders, which themselves

Methods

Results

Conclusion