Autoradiographic demonstration of an increase in muscarinic cholinergic receptors in cerebellar granule cells treated with tetrahydroaminoacridine.

The neurotrophic and neurosurviving effects of 9-amino-1,2,3,4-tetrahydroacridine (THA), a putative antidementia agent, were studied in cultured granule cells using biochemical and morphological methods. The addition of 30 microM THA to cultures grown in 15 mM K(+)-containing media markedly increased cell survival and enhanced [3H]N-methylscopolamine binding to muscarinic cholinergic receptors (mAChRs). Furthermore, receptor autoradiographic studies revealed that neuronal cells were labelled over both cell bodies and fibers by the [3H]receptor ligand. These observations provide direct evidence that THA promotes the expression of mAChR binding sites in differentiating cerebellar granule cells.