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Jordà EG, Verdaguer E, Morano A, Jiménez A, Canudas AM, Camins A, Pallàs M. Lithium prevents colchicine-induced apoptosis in rat cerebellar granule neurons. Bipolar Disord 2004: 6: 144–149. © Blackwell Munksgaard, 2004 Here we evaluated the neuroprotective effects of two well-known mood stabilizers, lithium and valproic acid (VPA), against colchicine neurotoxicity in cerebellar granule cells (CGNs). The CGNs were differentiated for 7 days, pretreated with lithium or VPA for 24 h and after colchicine 1 μM was added. Cellular damage was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) method and apoptosis in CGNs was characterized by chromatin condensation and DNA fragmentation. Incubation with lithium (1–5 mM) attenuated this apoptosis markedly, in a dose–dependent way however, the addition of VPA (0.5–2 mM) did not protect CGNs. Colchicine-induced apoptosis is mediated through the activation of caspase-3. An increase in caspase-3 activity was detected within 18 h and was blocked in presence of lithium 5 mM. Our data indicate that lithium treatment is selectively neuroprotective; however, in our experimental conditions VPA did not protect CGNs from apoptosis induced by colchicine. Our results support the hypothesis that distinct pathways mediate the neuroprotective effects of lithium and VPA. [ABSTRACT FROM AUTHOR]