Increased AMPA GluR1 receptor subunit labeling on the plasma membrane of dendrites in the basolateral amygdala of rats self‐administering morphine

Abstract

Glutamate-dependent synaptic plasticity is emerging as an important neural substrate of addiction. These drug-dependent neural adaptations may occur within brain systems that mediate reward, emotion, and cognitive function such as the amygdala complex. Modification of glutamate receptor targeting may be a key mechanism mediating neural plasticity; however, evidence for alteration of amygdala AMPA receptor localization in response to drug self-administration is lacking. High-resolution immunogold electron microscopic immunocytochemistry was used to compare surface and intracellular labeling of the calcium sensitive AMPA GluR1 receptor subunit in the basolateral (BLA) and central (CeA) nuclei of the amygdala in rats self-administering escalating doses of morphine or saline. Morphine self-administration was associated with regionally diverse effects on dendritic GluR1 targeting in the BLA and CeA. In the BLA of morphine self-administering animals, there was a significant increase in the proportion of immunogold particles for GluR1 on the plasma membrane of dendrites, particularly in association with extrasynaptic sites, which was most prominent in large (2-4 microm) profiles. In contrast, there were no significant differences in surface or intracellular immunogold labeling in the CeA between morphine self-administering and control animals. In both amygdala regions, GluR1 and the micro-opioid receptor, the major cellular target of morphine, were only infrequently colocalized. These results indicate that GluR1 targeting is a dynamic process that can be differentially affected in distinct amygdala regions in response to chronic self-administration of morphine. Homeostatic adaptations in the subcellular localization of calcium sensitive AMPA receptors within the BLA may be an important neural substrate for alterations in reward, autonomic function, and behavioral processes associated with opiate addiction.