The regulation of high-affinity choline uptake in vitro in rat cortical and hippocampal synaptosomes by beta-carbolines administered in vivo.

The effects of several beta-carboline derivatives on sodium-dependent high-affinity choline uptake (HACU) were investigated in rat hippocampus and cerebral cortex. HACU was measured in synaptosomal preparations from these areas after in vivo administration of the drugs. The convulsant, picrotoxin (6 mg/kg), stimulated HACU in both hippocampal and cortical synaptosomes. The convulsant inverse agonist benzodiazepine, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (5 mg/kg) stimulated hippocampal but not cortical HACU. However, other inverse agonists, methyl-beta-carboline-3-carboxylate (beta-CCM) (20 mg/kg) and ethyl-beta-carboline-3-carboxylate (beta-CCE) (20 mg/kg), stimulated HACU in the cortex but not in the hippocampus. The partial inverse agonist, N-methyl-beta-carboline-3-carboxylate (FG-7142) (20 mg/kg), inhibited cortical HACU and had no effect on hippocampal HACU. The antagonist beta-carboline, 3-hydroxymethyl-beta-carboline (3-HMC) (20 mg/kg), had no effect on either cortical or hippocampal HACU. None of these drugs displayed any effect on HACU when they were incubated directly in vitro with synaptosomal preparations at concentrations up to 100 microM, suggesting their activity is not directly on the cholinergic nerve terminal. The results suggest that beta-carbolines regulate hippocampal and cortical cholinergic activity as do other GABAergic drugs. However, unlike diazepam, which depresses cholinergic activity in both the hippocampus and the cortex the beta-carbolines differentiate between the hippocampus and cortex in their action.