Chronic treatment with anti-bipolar drugs suppresses glutamate release from astroglial cultures

Astroglial cells are fundamental elements of most neurological diseases, including bipolar disorders in which astrocytes show morphological and functional deficiency. Here we report the suppression of astroglial glutamate release by chronic treatment with three anti-bipolar drugs, lithium salt (Li+), carbamazepine (CBZ) and valproic acid (VPA). Release of glutamate was triggered by transient exposure of astrocytes to ATP (which activated purinoceptors) and 45 mM K+ (which depolarised cell membrane to ~−30 mV). In both types of stimulation glutamate release was regulated by Ca2+ entry through plasmalemmal channels and by Ca2+ release from the endoplasmic reticulum (ER) intracellular stores. Exposure of astroglial cultures to Li+, CBZ and VPA for 2 weeks led to a significant (more than 2 times) inhibition of glutamate release, which may alleviate the hyperactivity of the glutamatergic transmission in the brain of patients with bipolar disorders and thus contribute the underlying mechanism of drug action.