Changes in vesicular monoamine transporter (VMAT2) and synaptophysin in rat substantia nigra and prefrontal cortex induced by psychotropic drugs

We investigated the regulatory effect of the dopaminergic agent L-dopa, the mood stabilizer lithium and the nonselective monoamine oxidase inhibitor p henelzine on brain vesicular monoamine transporter (VMAT2) expression. Rats were treated chronically (21 days) with the three psychoactive drugs. VMAT 2 gene expression at the protein level was assessed in the prefrontal corte x and striatum by autoradiography with high-affinity [H-3]dihydrotetrabenaz ine ([H-3]TBZOH) binding and at the mRNA level in the substantia nigra pars compacta by in situ hybridization. In addition, the effect of various trea tments on the synaptophysin mRNA level was determined in the substantia nig ra by in situ hybridization. Chronic administration of L-dopa resulted in a significant decrease (28%, p < 0.05) in the density of [H-3]TBZOH binding in the prefrontal cortex but had no effect on VMAT2 and synaptophysin mRNA levels in the substantia nigra. Lithium treatment increased [H-3]TBZOH-spec ific binding in the prefrontal cortex (23%, p < 0.05) but had no effect on VMAT2 and synaptophysin mRNA levels. Phenelzine did not modulate VMAT2 gene expression but reduced the synaptophysin mRNA level (19%, p < 0.05). The m odulatory activities of these drugs, although relatively weak, may be relev ant to the drug-induced synaptic and neuronal plasticity as well as to the molecular and cellular pathophysiology of monoamine-related neuropsychiatri c disorders. Copyright (C) 2001 S. Karger AG, Basel.