Effects of kappa-opioid agonist U-50488 and p38 MAPK inhibitor SB203580 on the spike activity of pyramidal neurons in the basolateral amygdala
Research Results in Pharmacology(2024)
摘要
Introduction: Kappa-opioid receptor (KOR) signaling in the basolateral
amygdala (BLA) underlies KOR agonist-induced aversion. In this study, we aimed
to understand the individual and combined effects of KOR agonist U-50488 and
p38 MAPK inhibitor SB203580 on the spiking activity of pyramidal neurons in the
BLA to shed light on the complex interplay between KORs, the p38 MAPK, and
neuronal excitability. Materials and Methods: Electrophysiological experiments
were performed using the patch-clamp technique in the whole-cell configuration.
Rat brain slices containing the amygdala were prepared, and pyramidal neurons
within the BLA were visually patched and recorded in the current clamp mode.
The neurons were identified by their accommodation properties and neural
activity signals were amplified and analyzed. Using local perfusion, we
obtained three dose-response curves for: a) U-50488 (0.001-10 μM); b)
U-50488 (0.001-10 μM) in the presence of SB203580 (1 μM); and c)
U-50488 (0.01-10 μM) in the presence of SB203580 (5 μM). Results: After
the application of U-50488, pyramidal neurons had a higher action potential
firing rate in response to a current injection than control neurons (p<0.001).
The dose-dependent curves we obtained indicate that the combination of U-50488
and SB203580 results in non-competitive antagonism. This conclusion is
supported by the observed change in the curve`s slope with reduction in the
maximum effect of U-50488. Thus, it can be assumed that the increase in spike
activity of pyramidal neurons of the amygdala is mediated through the
beta-arrestin pathway. When this pathway is blocked, the spike activity reverts
to its baseline level. Conclusion: Our study found that the KOR agonist-induced
spiking activity of the BLA pyramidal neurons is mediated by the beta-arrestin
pathway and can be suppressed by the application of the p38 MAPK inhibitor
SB203580.
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关键词
kappa-opioid receptor,p38 mapk,amygdala,pyramidal neurons,patch clamp,electrophysiology,aversion
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