Fig. 2.

Most neurons in the inferior olivary nucleus degenerate after administration of the 3-AP regimen used in this study. In animals treated with ibogaine alone, inferior olive neurons remain intact and exhibit normal morphology (A, C); in contrast, profound loss of neurons is evident (B, D) in the inferior olive of rats that received the 3-AP regimen (3-acetylpyridine, harmaline, and nicotinamide; 13 d survival).A–D, Inferior olivary nucleus: Cam-kin II immunoreactivity at low (A, B) and high (C, D) magnification. E, Large neuronal cell bodies are shown with Nissl stain of rats (E), whereas smaller profiles are glial cells. F, After the 3-AP regimen, neuronal profiles in the inferior olive are absent, and this nucleus has become densely populated with small glial cell bodies. The inferior olive is gliotic because of proliferation of astrocytes and microglia that were activated in response to degeneration of inferior olive neurons. Using a marker for microglial cells (G, H), only lightly stained, resting microglia are observed in the inferior olive from an ibogaine-treated rat (G); in contrast, after the 3-AP regimen, densely packed activated microglia occupy the site of the former inferior olivary nucleus (H) and demarcate the different subregions that were present in this nucleus. Cytochemical markers and stains: A–D, Cam-kin II immunocytochemistry for inferior olive neurons; E, F, Nissl stain of inferior olive; G, H, to identify microglia, the inferior olive is stained with antibody (OX42) that recognizes the complement receptor 3B. This receptor is expressed at moderate levels by quiescent microglia and is greatly increased in activated microglia in response to neuronal injury or degeneration. Scale bars:A–H, 100 μm.