INCREASED MIDBRAIN DOPAMINERGIC CELL-ACTIVITY FOLLOWING 2'CH3-MPTP-INDUCED DOPAMINERGIC CELL LOSS - AN INVITRO ELECTROPHYSIOLOGICAL STUDY

Several days after the administration of 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydropyridine (2′CH3-MPTP) to the BALB/cJ mouse there is a loss of midbrain dopaminergic neurons, a reduction of forebrain dopamine (DA) content, and an elevation in forebrain DA turnover. The purpose of the present study was to determine whether the increase in forebrain DA turnover is related to an increase in dopaminergic neuronal activity. In vitro extracellular single unit recordings were made from midbrain dopaminergic neurons in the substantia nigra pars compacta (nucleus A9) and ventral tegmental area (nucleus A10) of BALB/cJ mice. The experimental animals were treated intraperitoneally with 40, 50 or 55 mg/kg 2′CH3-MPTP and killed 7-15 days later. Forebrain DA concentrations were decreased below control values by the two higher toxin doses in the caudate-putamen (67% and 78%, respectively), but not in the nucleus accumbens. DA turnover increased more than 2-fold in the caudate-putamen, but was unchanged in the nucleus accumbens. Nucleus A9 cells, in the 2′CH3-MPTP-treated animals, exhibited a 3-fold increase in the number of spontaneously active cells, and an 84% increase in basal firing rates. There was also a positive correlation between the A9 cell firing rates, and the DA turnover in the striatum of the toxin-treated mice. Nucleus A10 cells, in the 2′CH3-MPTP-treated animals, exhibited neither changes in number of spontaneously active cells nor changes in firing rates. These data indicate that increases in forebrain DA turnover, which follow significant losses of midbrain dopaminergic neurons, are correlated with increases in both the (1) number of spontaneously active midbrain dopaminergic cells, and (2) basal firing rates of these cells. © 1990.