Chronic administration of morphine is associated with a decrease in surface AMPA GluR1 receptor subunit in dopamine D1 receptor expressing neurons in the shell and non-D1 receptor expressing neurons in the core of the rat nucleus accumbens

Abstract

The nucleus accumbens (Acb) is an extensively studied neuroanatomical substrate of opiate reward and the neural plasticity associated with chronic opioid use. The cellular mechanisms mediating opioid-dependent plasticity are uncertain, however AMPA-type glutamate receptor trafficking in dopamine D1 dopamine receptor (D1R) expressing neurons may be a potential cellular pathway for these adaptations, although there is no evidence for this possibility. Immunogold electron microscopy was used to quantify the surface expression of the AMPA GluR1 subunit in dendritic profiles of neurons in the Acb in response to intermittent 14-day non-contingent injections of escalating doses of morphine, a model that parallels opioid self-administration. To determine if changes in GluR1 trafficking occurred in neurons potentially sensitive to dopamine-induced D1R activation, immunoperoxidase labeling of D1R was combined with immunogold labeling of GluR1.Immunogold quantification was performed in two distinct Acb subregions, the shell, an area involved in processing incentive salience related to rewarding stimuli, and the core, an area involved in rewardseeking behaviors. We provide the first report that chronic morphine administration is associated with a receptor-phenotypic decrease in surface trafficking of GluR1 in Acb subregions. When compared to saline injected animals, morphine produced a decrease in plasma membrane GluR1 labeling in medium-and large-size D1R expressing dendritic profiles in the Acb shell. In contrast, in the Acb core, surface GluR1 was decreased in small-size dendrites that did not express the dopamine receptor. These results indicate that chronic intermittent injection of escalating doses of morphine is accompanied by ultrastructural plasticity of GluR1 in neurons that are responsive to glutamate and dopamine-induced D1R activation in the Acb shell, and neurons capable of responding to glutamate but not D1R receptor stimulation in the Acb core. Thus, AMPA receptor trafficking associated with chronic opiate exposure in functionally distinct areas of the Acb may be distinguished by D1R receptor activation, suggesting the potential for differing neural substrates of reward and motor aspects of addictive processes involving glutamate and dopamine signaling.

The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction

“…Microinjection of ionotropic glutamate receptor antagonists MK-801 or DNQX into the VTA attenuated the reinforcement effect in heroin addiction (Xi and Stein, 2002b). Chronic intermittent injection of escalating doses of morphine is accompanied by ultrastructural plasticity of GluR1 in neurons that are responsive to glutamate, activation of DA-induced D1 dopamine receptor in the NAc shell, and activation of neurons capable of responding to glutamate but not to D1 dopamine receptor stimulation in the NAc core (Glass et al, 2008). These results indicate that glutamate released in the central nervous system plays an important role in opioid withdrawal behaviors and that the iGluRs are involved in the process.…”

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

“…It has been reported that chronic morphine treatment can cause functional changes in dopamine-containing neurons that spread widely within these regions and results in an increase in neuronal activity and dopamine release from their nerve terminals (Berridge and Robinson, 1998;Spanagel and Weiss, 1999;Schultz, 2000). In addition, morphine-induced adaptive changes in postsynaptic parts of dopaminergic projections in NAc and PFC also have been reported (Ito et al, 2007;Glass et al, 2008;Narita et al, 2010). However, little is known about adaptive changes in dopaminergic signaling in BLA upon chronic morphine treatment.…”

Narp Deletion Blocks Extinction of Morphine Place Preference Conditioning

“…For example, a single dose of morphine increases synaptic strength at excitatory synapses in the ventral tegmental area (VTA; Saal et al, 2003) and produces a delayed increase in glutamate receptor responses in the nucleus accumbens (NAc; Jacobs et al, 2005). Furthermore, repeated morphine administration induces structural changes in dendritic processes in NAc and prefrontal cortex (PFC; Robinson and Kolb, 1999), as well as changes in the level of expression and subcellular localization of GluR1 receptors (Fitzgerald et al, 1996;Glass et al, 2005Glass et al, , 2008.…”