Food restriction modulates amphetamine-conditioned place preference and nucleus accumbens dopamine release in the rat

Food restriction has been shown to increase self-administration of psychostimulants, including cocaine and amphetamine (AMPH). Consistent with this, food-restricted rats are more sensitized to the rewarding effects of cocaine as measured by conditioned place preference (CPP). This study investigated whether moderate food restriction in rats (15 g/day) results in an increased CPP, relative to ad libitum-fed controls, to a second psychostimulant, AMPH. Conditioning trials consisted of six alternating injections of i.p. AMPH (0.425-6.8 mg/kg) and i.p. saline, paired with distinct environments. On Day 7, a drug-free 20-min choice test for environment was carried out to assess CPP. 0.85 mg/kg AMPH significantly increased CPP in food-restricted vs. ad libitum-fed rats. At 1.7 and 3.4 mg/kg AMPH, food-restricted rats showed decreased CPP, but increased locomotor activity, relative to ad libitum fed controls. To evaluate whether an alteration in extracellular fluid DA levels in the nucleus accumbens (NAc) core could account for these behavioral alterations, DA release was measured by microdialysis. DA release to a single acute i.p. injection of either 0.85 or 1.7 mg/kg AMPH was comparable in food-restricted and ad libitum fed rats. However, ad libitum fed rats demonstrated conditioned DA release after an AMPH conditioning paradigm analogous to the CPP paradigm, whereas food-restricted rats demonstrated no conditioned DA release. In conclusion, altered DA release in the nucleus accumbens core is not a primary effect of moderate food restriction and cannot completely account for either the altered CPP behavior or enhanced locomotor activity observed in this study.