Figure 1.
Salsolinol-induced stimulation of dopaminergic (DA) neurons is attenuated by APV and DNQX.
A1, Traces illustrate spike discharge at the times indicated in A2. A2, Time course of the increase in the ongoing pacemaking firing rate, recorded from a current-clamped DA neuron in the posterior ventral tegmental area (p-VTA) of a rat, by 0.1 µM salsolinol. B1, Traces obtained at the times indicated in B2. B2, Time course of the effect of salsolinol on the firing rate of a DA neuron in the presence of APV (50 µM) and DNQX (20 µM), the antagonists of NMDA and AMPA receptors. C, Summary plot of decease in firing rate by APV + DNQX. D, Summary plot (means ± S.E.M.) of increase in firing rate of p-VTA DA neurons induced by salsolinol (0.1 µM) in ACSF is larger than that in the APV+DNQX. Numbers in bars indicate numbers of neurons tested. *P<0.05, **P<0.01, paired t-test for salsolinol vs. pre-salsolinol control. Unpaired t-test for salsolinol vs. APV+DNQX+salsolinol.
Figure 2.
Salsolinol increases frequency of spontaneous EPSCs (sEPSCs) recorded from p-VTA DA neurons.
EPSCs were recorded in the presence of bicuculline (10 µM) at a holding potential of −70 mV. A1, Traces obtained at the times indicated in A2. A2, Time course of 0.1 µM salsolinol-induced enhancement of sEPSC frequency in one experiment. B, C, Cumulative probability plots of data from the same cell show effects of salsolinol (0.1 µM) on sEPSC frequency (B) and amplitudes (C). Insets: mean data (± S.E.M., from seven neurons). *P<0.05, **P<0.01, paired t-test for salsolinol vs. pre-salsolinol control.
Figure 3.
Tetrodotoxin (TTX) abolishes Salsolinol's increase of sEPSCs.
The miniature EPSCs (mEPSCs) were recorded in p-VTA DA neurons at a holding potential of −70 mV, in the presence of bicuculline (10 µM) and TTX (0.5 µM). A1, Traces obtained at the times indicated in A2. (A2) Time course of salsolinol-induced changes of mEPSC frequency in one experiment. B, C, Cumulative probability plots of inter-event intervals between mEPSCs (B) and their amplitudes (C). Insets: mean data (± S.E.M., from six neurons) confirm the absence of significant effect of salsolinol (0.1 µM) on the frequency and the amplitude of mEPSCs. *P<0.05, paired t-test for salsolinol vs. pre-salsolinol control.
Figure 4.
Salsolinol increases amplitude and decreases paired-pulse ratio (PPR) of evoked EPSCs (eEPSCs) recorded from p-VTA DA neurons.
eEPSCs were recorded in the presence of bicuculline (10 µM) at a holding potential of −70 mV. A, Salsolinol (0.1 µM) sharply increased the peak amplitude of eEPSC1 and had minimal effect on that of eEPSC2 evoked by paired stimulation (at 50- ms interval) within the VTA, and hence reduced the PPR (EPSC2/EPSC1). B, Time course of salsolinol-induced enhancement of eEPSC1 amplitude in one experiment. C, Summary of salsolinol-induced changes (%) in eEPSC1 amplitude and PPR (Mean ± SEM, from eleven neurons). *P<0.05, **P<0.01, paired t-test for salsolinol vs. pre-salsolinol control.
Figure 5.
The D1R antagonist SKF 83566 eliminates salsolinol's augmentation of eEPSCs.
A, Current traces show that salsolinol did not change the amplitude of eEPSC1 and PPR in the presence of 10 µM SKF 83566. B, Time course of salsolinol-induced changes of eEPSC1 amplitude in nine experiments. C, Summary of salsolinol-induced changes (%) in eEPSC1 amplitude and PPR in the presence of SKF 83566 (data from nine cells). *P<0.05, **P<0.01, paired t-test for salsolinol application vs. pre-salsolinol control.
Figure 6.
SKF83566 attenuates salsolinol-induced excitation of p-VTA DA neurons.
A, Ongoing firing in the presence of SKF83566 (10 µM), recorded from a current-clamped p-VTA DA neuron, was increased by salsolinol (0.1 µM). B, Pooled data show that in the presence of SKF83566, salsolinol induced an increase in firing rate of p-VTA DA neurons from thirteen cells. C, Summary (means ± S.E.M.) of the effects of salsolinol (0.1 µM) on DA neuron firing rate in the absence (ACSF) and presence of SKF 83566 (SKF 63566). Numbers of cells are indicated in the brackets. *P<0.05 by un-paired t-test, salsolinol vs. SKF 83566+salsolinol.