Dopamine attenuates evoked inhibitory synaptic currents in central amygdala neurons - PubMed (original) (raw)

Dopamine attenuates evoked inhibitory synaptic currents in central amygdala neurons

Jennifer C Naylor et al. Eur J Neurosci. 2010 Dec.

Abstract

The central nucleus of the amygdala (CeA) plays a critical role in regulating the behavioral, autonomic and endocrine response to stress. Dopamine (DA) participates in mediating the stress response and DA release is enhanced in the CeA during stressful events. However, the electrophysiological effects of DA on CeA neurons have not yet been characterized. Therefore, the purpose of this study was to identify and characterize the effect of DA application on electrophysiological responses of CeA neurons in coronal brain sections of male Sprague-Dawley rats. We used whole-cell patch-clamp electrophysiological techniques to record evoked synaptic responses and to determine basic membrane properties of CeA neurons both before and after DA superfusion. DA (20-250 μM) did not significantly alter membrane conductance over the voltage range tested. However, DA significantly reduced the peak amplitude of evoked inhibitory synaptic currents in CeA neurons. Pretreatment with the D(2) receptor antagonist eticlopride failed to significantly block the inhibitory effects of DA. In contrast, pretreatment with the D(1) receptor antagonist SCH-23390 significantly reduced the effects of DA on evoked inhibitory neurotransmission in these neurons. Moreover, bath superfusion of the specific D(1) receptor agonist SKF-39393, but not the D(2) receptor agonist quinpirole, significantly reduced peak amplitude of evoked inhibitory synaptic events. DA reduced the frequency of miniature IPSCs without altering the amplitude, while having no effect on the amplitude of IPSCs elicited by pressure application of GABA. These results suggest that DA may modulate inhibitory synaptic transmission in CeA through D(1) receptor activation primarily by a presynaptic mechanism.

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Figures

Figure 1

Representative waveforms of evoked inhibitory potentials during application of DA and specific DA antagonists and agonists. A. IPSC waveforms of baseline, DA (50 μM), and washout (scale 25 pA, 25 msec). B. Dose-response curve for DA on evoked IPSCs. C. Time course of DA (50 μM) effect (applied for the period of bar) on normalized evoked IPSC amplitudes (n=14).

Figure 2

DA inhibits inhibitory currents through the D1 receptor subtype in CeA neurons. A. IPSC waveforms after pretreatment with eticlopride (50 μM), DA, and washout. B. IPSC waveforms after pretreatment with SCH-23390 (20 μM), DA, and washout. C. Representative waveforms of evoked IPSC activity during baseline, superfusion of SKF-38393 alone, and co-superfusion of SKF-38393 & quinpirole. Scale: 12 pA, 10 msec. D. Bar graph depicting percent change in IPSC peak amplitude during superfusion of the following chemicals (from left to right): DA (50 μM; 30.58 ± 3.34%, p<.01, n=14); DA following pretreatment with the D2 receptor antagonist eticlopride (50 μM) (24.44 ± 2.58%, p< .001, n=11); DA following pretreatment with the D1 receptor antagonist, SCH-23390 (20 μM) (8.85 ± 5.69%, n=9); D1 receptor agonist, SKF-38393 (80 μM; 21.00± 3.33%, p<.000, n=10); D2 receptor agonist quinpirole (80 μM, 3.83 ± 3.85%, n=6); co-application of 50 μM DA and WAY-100635 (50 nM) (21.21 ± 5.62, p<.02, n=5); apomorphine (50 μM); 60.17±13.55%, p<.03, n=3).

Figure 3

DA has little overall effect on steady state membrane conductance of CeA neurons even at very high concentrations. Current pulses (600 msec) were delivered at 10 pA steps. A. Graph of current-voltage relationship after application of 50 μM DA (n=7). B. 100 μM DA (n=7). C. 250 μM DA (n=7). D. Representative traces of current-voltage relationship before (upper) and after (lower) superfusion of 50 μM DA (scale 50 mV, 50 msec).

Figure 4

DA reduced the frequency of spontaneous mIPSCs. A. TTX -insensitive mIPSCs were isolated from CeA neurons held at −70mV. Bath application of 75 μM DA reduced the frequency. B. Cumulative probability analysis indicated that DA attenuated the frequency of mIPSCs (K-S test, p<0.001) but had no effect on the amplitude (K-S test, p>0.05). C. Bar graph showing the mean percent inhibition by 75μM DA of the frequency (n=10, paired t-test, p<0.05) and amplitude of mIPSCs (paired t-test, p>0.05).

Figure 5

DA did not affect the post-synaptic GABA currents elicited by direct pressure application of GABA. A. Representative traces of whole cell currents evoked by puffing 100 nM GABA on the soma of CeA neurons before and during application of DA are shown. BMI reversibly blocked GABA-evoked whole cell currents. (Scale bar 1sec/100pA). B. There was no significant change in mean amplitude of GABA-evoked currents between baseline and DA application (one-way ANOVA, p>0.05).

References

1. Andersen PH, Jansen JA. Dopamine receptor agonists: Selectivity and dopamine D1 receptor efficacy. Eur J Pharmacol. 1990;188:335–347. - PubMed
1. Asan E. Ultrastructural features of tyrosine-hydroxylase-immunoreactive afferents and their targets in the rat amygdala. Cell Tissue Res. 1997;288:449–469. - PubMed
1. Bissiere S, Humeau Y, Luthi A. Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nat Neurosci. 2003;6:587–592. - PubMed
1. Boyson SJ, McGonigle P, Molinoff PB. Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J Neurosci. 1986;6:3177–3188. - PMC - PubMed
1. Coco ML, Kuhn CM, Ely TD, Kilts CD. Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam. Brain Res. 1992;590:39–47. - PubMed

Dopamine attenuates evoked inhibitory synaptic currents in central amygdala neurons - PubMed (original) (raw)