Effect of dopamine and baclofen on N-methyl-d-aspartate-induced burst firing in rat ventral tegmental neurons

Intracellular microelectrode recordings were made from dopamine-containing neurons of the ventral tegmental area or substantia nigra zona compacta in rat brain slices in vitro. The firing pattern of the neurons was switched from a tonic, single-spike pattern to a burst firing mode by adding N-methyl-d-aspartate (20 μM) to the supervising solution; after adding tetrodotoxin the membrane potential underwent rhythmical oscillations of 20-40 mV at 0.5-2 Hz. Baclofen (1 μM) and dopamine (30 μM) hyperpolarized the neurons; when the potential was restored to its original level, the oscillations of potential and/or burst firing were not observed, but the tonic firing pattern was restored. These effects of baclofen and dopamine were prevented by barium (1 mM), which also prevented the membrane hyperpolarization. Oscillations of membrane current of a similar frequency were observed when the somatic membrane was voltage-clamped at -60 mV; these were also blocked by barium (1 mM). It is concluded that the oscillations in membrane potential observed with N-methyl-d-aspartate are generated predominantly at a dendritic location which is not voltage-clamped with an electrode at the soma. Baclofen and dopamine inhibit the oscillations by increasing the potassium conductance and hyperpolarizing the dendrites.