Inhibitory effects of dopamine agonists on pain-responsive neurons in the central nucleus of the amygdala

Abstract

The central nucleus of the amygdala (CeA) is a heterogenous region of primarily GABAergic neurons that contributes to numerous behaviors, including fear learning, feeding, reward, and pain. Dopaminergic inputs to the CeA have been shown to regulate many of these behaviors, but how dopamine exerts these effects at the cellular level has not been well characterized. We used the Targeted Recombination in Active Populations (TRAP) mouse line to fluorescently label pain-responsive CeA neurons, and then targeted these cells for patch-clamp recordings in acute slices to test the effects of dopamine agonists. The D1 agonist SKF-38393 and D2 agonist quinpirole both had inhibitory effects, reducing the input resistance and evoked firing and increasing rheobase of labeled CeA neurons. Both agents also inhibited the NMDA component of excitatory postsynaptic currents (EPSCs) evoked by basolateral amygdala (BLA) stimulation, but did not affect the AMPA component. D1 activation, but not D2, also appeared to have a presynaptic effect, increasing the frequency of spontaneous EPSCs. These results provide new insights into how dopamine regulates activity within pain-responsive CeA networks. NEW & NOTEWORTHYDopamine is known to regulate activity within the central amygdala (CeA), an important region for central pain processing. However, its effects at the cellular level have not been well characterized. We targeted pain-responsive CeA neurons for patch-clamp recordings to examine the cellular and synaptic effects of D1 and D2 agonists. Activation of either D1 or D2 receptors induced inhibitory effects, suggesting dopamine signaling in CeA dampens pain-related activity and could be a target for analgesics.