THE DEPLETION OF BRAIN-SEROTONIN LEVELS BY PARA-CHLOROPHENYLALANINE ADMINISTRATION SIGNIFICANTLY ALTERS THE ACTIVITY OF MIDBRAIN DOPAMINE CELLS IN RATS - AN EXTRACELLULAR SINGLE-CELL RECORDING STUDY

In this study, we examined the effect of 5-HT depletion produced by th e acute administration of para-chlorophenylalanine (PCPA) on the numbe r of spontaneously active dopamine (DA) cells in the ventral tegmental area (VTA or A10) and substantia nigra pars compacta (SNC or A9) in t he rat. We also determined the effect of PCPA administration on the sp ike discharge pattern of midbrain DA cells. This was accomplished usin g standard extracellular single cell recording techniques. The adminis tration of PCPA (400 mg/kg, i.p., 24 h before the experiment) produced a significant decrease in the number of spontaneously active DA cells in both the A9 (52%) and A10 (63%) areas compared to controls. The bu rst firing analysis indicated that there was a significant increase in the mean interspike interval of A9 and A10 DA neurons in PCPA treated animals compared to controls. Furthermore, a decrease in the percenta ge of A10 DA neurons exhibiting a burst firing pattern and the number of bursts was observed in the PCPA treated animals compared to control s. The intravenous (i.v.) administration of 5-hydroxytryptophan (40 mg /kg) and the peripheral aromatic acid decarboxylase inhibitor benseraz ide (10 mg/kg) which restores 5-HT content, reversed the decrease in t he number of spontaneously active A9 and A10 DA neurons, as well as th e decrease in the percentage of A10 DA neurons exhibiting a bursting p attern. In contrast, the i.v. administration of benserazide (10 mg/kg) and L-DOPA (40 mg/kg) did not reverse the decrease in the number of s pontaneously active midbrain DA neurons produced by PCPA treatment. Th e pretreatment of animals with PCPA did not alter the sensitivity of s pontaneously active A9 or A10 DA cells to the intravenous administrati on of (+)-apomorphine (1-32 mu g/kg) compared to controls. Overall, ou r results indicate that the depletion of brain 5-HT by PCPA produces a decrease in the activity of midbrain DA cells, suggesting that endoge nous 5-HT is required to maintain DA tone. (C) 1996 Wiley-Liss, Inc.