Elsevier

Neuroscience

Volume 165, Issue 4, 17 February 2010, Pages 1074-1086
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2009.11.015Get rights and content

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.

Section snippets

Subjects and surgical procedures

All subjects were male Sprague–Dawley rats (Taconic Farms, Germantown, NY, USA) weighing 350–400 g at the time of arrival in the central animal facility where they were housed in individual plastic cages, with free access to Purina rat chow (St. Louis, MO, USA) and water unless otherwise noted. The animal room was maintained on a 12-h light/dark cycle, with lights on at 07:00 h. Approximately half the subjects in each experiment were placed on a chronic food restriction regimen whereby daily

Experiments 1 and 2: GluR1 phosphorylation under basal and stimulated conditions in AL and FR rats

Following vehicle administration, NAc tissue samples obtained from AL and FR rats did not differ in abundance of total GluR1 protein, phospho-Ser845 (Fig. 1), or phospho-Ser831 GluR1 (Fig. 2). Systemic administration of the D-1 DA receptor agonist, SKF-82958 (1.0 mg/kg i.p.), increased GluR1 phosphorylation on Ser845 in NAc (F1,16=24.4, P<.001). Feeding groups differed (F1,16=7.1, P<.02), and an interaction between drug treatment and feeding condition (F1,16=4.8, P<.05), followed by Fisher's

Discussion

The enhanced rewarding effects of abused drugs in FR animals have been demonstrated in self-administration, conditioned placed preference, and ICSS paradigms (Carroll and Meisch, 1984, Bell et al., 1997, Cabeza de Vaca and Carr, 1998, Cabeza de Vaca et al., 2004, Carr et al., 2000). The mechanistic importance of NAc neuroadaptations downstream of D-1 DA receptor stimulation in these behavioral effects is suggested by findings that FR enhances SKF-82958-induced activation of several

Acknowledgments

Supported by DA003956 (KDC) and MH067229 (EBZ) from NIH, and a seed grant in the Center of Excellence on Addiction from the New York University Langone Medical Center.

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