AMPA receptor subunit GluR1 downstream of D-1 dopamine receptor stimulation in nucleus accumbens shell mediates increased drug reward magnitude in food-restricted rats

Abstract

Previous findings suggest that neuroadaptations downstream of D-1 dopamine (DA) receptor stimulation in nucleus accumbens (NAc) are involved in the enhancement of drug reward by chronic food restriction (FR). Given the high co-expression of D-1 and GluR1 AMPA receptors in NAc, and the regulation of GluR1 channel conductance and trafficking by D-1-linked intracellular signaling cascades, the present study examined effects of the D-1 agonist, SKF-82958, on NAc GluR1 phosphorylation, intracranial electrical self-stimulation reward (ICSS), and reversibility of reward effects by a polyamine GluR1 antagonist, 1-NA-spermine, in ad libitum fed (AL) and FR rats. Systemically administered SKF-82958, or brief ingestion of a 10% sucrose solution, increased NAc GluR1 phosphorylation on Ser845, but not Ser831, with a greater effect in FR than AL rats. Microinjection of SKF-82958 in NAc shell produced a reward-potentiating effect that was greater in FR than AL rats, and was reversed by co-injection of 1-NA-spermine. GluR1 abundance in whole cell and synaptosomal fractions of NAc did not differ between feeding groups, and microinjection of AMPA, while affecting ICSS, did not exert greater effects in FR than AL rats. These results suggest a role of NAc GluR1 in the reward-potentiating effect of D-1 DA receptor stimulation and its enhancement by FR. Moreover, GluR1 involvement appears to occur downstream of D-1 DA receptor stimulation rather than reflecting a basal increase in GluR1 expression or function. Based on evidence that phosphorylation of GluR1 on Ser845 primes synaptic strengthening, the present results may reflect a mechanism via which FR normally facilitates reward-related learning to re-align instrumental behavior with environmental contingencies under the pressure of negative energy balance.

Nucleus Accumbens and Dopamine-Mediated Turning Behavior of the Rat: Role of Accumbal Non-dopaminergic Receptors

“…Moreover, stimulation of dopamine D 1 receptors in the Nacc shell phosphorylates AMPA receptors, thereby strengthening the function of AMPA receptors (40). Therefore, an alternative explanation concerning the above-mentioned results is that NMDA and AMPA receptors postsynaptically modulate the dopamine function, possibly via D 1 receptors.…”

Augmentation of Heroin Seeking Following Chronic Food Restriction in the Rat: Differential Role for Dopamine Transmission in the Nucleus Accumbens Shell and Core

“…Moreover, we have recently reported that blockade of DA D1-, but not D2-like receptors, attenuated acute food deprivation-induced reinstatement of heroin seeking (Tobin et al, 2013). In addition, chronic food restriction increases synaptic plasticity in NAc cells expressing DA D1-like, but not D2-like, receptors (Carr et al, 2003(Carr et al, , 2010. Consequently, here we administered a DA D1-like receptor antagonist into the NAc shell and core to determine if DA transmission via the D1-like receptors is causally related to the augmentation of heroin-seeking induced by chronic food restriction.…”

Ca2+-permeable AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) Receptors and Dopamine D1 Receptors Regulate GluA1 Trafficking in Striatal Neurons

“…Activation of dopamine D1 receptors (D1Rs) has been shown to increase GluA1 Ser-845 phosphorylation and induce membrane insertion in striatal neurons through a PKA-dependent mechanism (37)(38)(39)(40). Nitric oxide signaling plays a prevalent role in modulating MSN excitability (41), and cGMP plays an important role in this regulation (42,43), but the mechanisms by which it regulates MSN synapses are unknown.…”