Signal Transduction in Astrocytes during Chronic or Acute Treatment with Drugs (SSRIs, Antibipolar Drugs, GABA-ergic Drugs, and Benzodiazepines) Ameliorating Mood Disorders

Chronic treatment with fluoxetine or other so-called serotonin-specific reuptake inhibitor antidepressants (SSRIs) or with a lithium salt “lithium”, carbamazepine, or valproic acid, the three classical antibipolar drugs, exerts a multitude of effects on astrocytes, which in turn modulate astrocyte-neuronal interactions and brain function. In the case of the SSRIs, they are to a large extent due to 5-HT(2B)-mediated upregulation and editing of genes. These alterations induce alteration in effects of cPLA(2), GluK2, and the 5-HT(2B) receptor, probably including increases in both glucose metabolism and glycogen turnover, which in combination have therapeutic effect on major depression. The ability of increased levels of extracellular K(+) to increase [Ca(2+)](i) is increased as a sign of increased K(+)-induced excitability in astrocytes. Acute anxiolytic drug treatment with benzodiazepines or GABA(A) receptor stimulation has similar glycogenolysis-enhancing effects. The antibipolar drugs induce intracellular alkalinization in astrocytes with lithium acting on one acid extruder and carbamazepine and valproic acid on a different acid extruder. They inhibit K(+)-induced and transmitter-induced increase of astrocytic [Ca(2+)](i) and thereby probably excitability. In several cases, they exert different changes in gene expression than SSRIs, determined both in cultured astrocytes and in freshly isolated astrocytes from drug-treated animals.