Nucleus accumbens AMPA receptor involvement in cocaine-conditioned place preference under different dietary conditions in rats

Abstract

Rationale When ad libitum fed (AL) rats undergo cocaine place preference conditioning (CPP) but are switched to food-restriction (FR) for testing, CPP is enhanced and preference scores correlate with phosphorylation of AMPA receptor GluA1 at Ser845 in nucleus accumbens (NAc) core. Objectives The present study tested whether a similar association exists in AL rats, and whether an inhibitor of Ca2+-permeable AMPARs blocks CPP expression in either diet group. Materials and methods In Experiments 1-3, AL rats were conditioned with cocaine (12.0 mg/kg, i.p.). Three weeks later, CPP was tested daily and brains were harvested after the 5th test. Western analyses were used to probe for levels of AMPA receptors in NAc. In Experiment 4, AL rats were conditioned, half were switched to FR for testing, and half in each diet group received NAc core microinjection of NASPM (25.0 μg) prior to each test. Results In Experiment 1, CPP expression in AL rats was associated with elevated pSer845-GluA1, GluA1 and GluA2 in NAc. In Experiment 2, the correlation between pSer845-GluA1 and CPP was localized to NAc core. In Experiment 3, pSer845-GluA1 following a CPP test was higher in NAc synaptic membranes of FR relative to AL rats. In Experiment 4, NASPM blocked CPP expression in both diet groups. Conclusions Results support a scheme in which pSer845-GluA1 in NAc core underlies expression of cocaine CPP, and does so by stabilizing or trafficking Ca2+-permeable AMPARs to the synaptic membrane. The more robust CPP of FR rats may result from upregulation of stimulus-induced pSer845-GluA1.

Effects of food restriction on expression of place conditioning and biochemical correlates in rat nucleus accumbens

“…These correlations are mainly reflective of the diet group differences, in as much as regression analyses confined to individual diet groups were positive but nonsignificant. This differs from previous cocaine CPP studies in which this correlation in NAc core was significant within each diet group (Zheng et al 2013, 2015). There were no significant correlations between total GluA1, pERK1, or pERK2 and behavior.…”

“…This observation is concordant with reports that food restriction enhances reinstatement of cocaine- (Carroll 1985) and heroin-seeking (D’Cunha et al 2013) in self-administration protocols. The cocaine CPP studies have also revealed that the persistent CPP in food restricted subjects is not affected by the temporal relation between the most recent meal and testing, or meal-entrained levels of blood-borne metabolic hormones (Zheng et al 2013), but correlates with phosphorylation of the glutamatergic AMPA receptor GluA1 subunit at Ser845 in nucleus accumbens core, and is blocked by accumbens core microinjection of Naspm, a selective antagonist of calcium-permeable AMPA receptors (Zheng et al 2013; Zheng et al, 2015). This parallels findings relating to increased unconditioned drug reward in food restricted rats, though the accumbens subdivision implicated is the shell (Carr et al 2010; Peng et al 2014).…”

Modulatory effects of Ampicillin/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine-seeking behavior

“…injections of cocaine induced place preference and increased locomotor activity as well as that cocaine CPP was extinguished after eight saline i.p. injection (24, 61, 75–79). The acute locomotor responses to drugs of abuse, including cocaine, are mainly dependent on the mesolimbic and nigrostriatal dopaminergic systems, which are known to be regulated by the glutamatergic system (80).…”

Nucleus accumbens AMPA receptor trafficking upregulated by food restriction: an unintended target for drugs of abuse and forbidden foods

“…In order to test the contribution of these receptors to behavior, Naspm was microinjected into NAc shell and shown to selectively reverse the enhancing effect of FR on rewarding effects of a D-1 agonist and d-amphetamine [24,25]. When microinjected into NAc core, Naspm blocked the robust and persistent expression of cocaine CPP in FR animals [48]. Overall, these results indicate that FR-induced synaptic incorporation of CP-AMPARs plays a fundamental role in the enhancement of behavioral responsiveness to psychostimulant drugs, associated environments, and specifically D-1 receptor stimulation.…”