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 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (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 Ca(2+)-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 fifth 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 1-naphthylacetyl spermine (NASPM (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 Ca(2+)-permeable AMPARs to the synaptic membrane. The more robust CPP of FR rats may result from upregulation of stimulus-induced pSer845-GluA1.
Keywords: Cocaine; Conditioned place preference; Food restriction; GluA1; Nucleus accumbens.