Chronic Morphine Treatment Switches the Effect of Dopamine on Excitatory Synaptic Transmission from Inhibition to Excitation in Pyramidal Cells of the Basolateral Amygdala

Abstract

Dopaminergic signaling in the basolateral amygdala (BLA) is important for drug-stimulus learning that triggers relapse to drug-seeking behavior. However, little is known about adaptive changes in this signaling pathway upon chronic morphine treatment. In this paper, we observed the influence of chronic morphine treatment on the effect of dopamine (DA) on the excitatory transmission in the pyramidal cells of BLA in slices with the whole-cell patch-clamp method. We also studied its mechanism and significance with pharmacological approaches combined with biochemical and behavioral techniques. The results showed that chronic morphine exposure switched the effect of DA on the excitatory synaptic transmission from inhibition to excitation; the chronic morphine-induced switching action on the effect of DA was due to its influence on D1 receptors; the site of the effect of chronic morphine treatment on D1 receptors was at presynaptic locus; chronic morphine treatment induced a significant increase in the amount of D1 receptor expression in the synaptosomes and synaptosomal membrane fraction from BLA; the enhancement of presynaptic glutamate release by D1 receptor agonist upon chronic morphine treatment was dependent on the activation of cAMP-dependent protein kinase; and the intra-BLA injection of D1 receptor antagonist canceled the conditioned place aversion (CPA) in morphine-dependent rats. In conclusion, chronic morphine treatment switches the effect of DA on the excitatory synaptic transmission from inhibition to excitation by the presynaptic D1 receptor amount increase-mediated glutamate release in the pyramidal cells of BLA and the blockade of D1 receptors in BLA cancels CPA in morphine-dependent rats.