Effect of chronic food restriction on Fos-like immunoreactivity (FLI) induced in rat brain regions by intraventricular MK-801

The noncompetitive NMDA antagonist, MK-801, produces stimulant and rewardin g effects that are mediated by a combination of dopamine-dependent and -ind ependent mechanisms. It was recently demonstrated that, similar to amphetam ine, the rewarding and locomotor effects of intraventricular (i.c.v.) MK-80 1 are potentiated by chronic food restriction. Because food restriction als o increases c-Fos expression induced by i.c.v. amphetamine in several subco rtical dopamine (DA) terminal areas, Fos-like immunoreactivity (FLI) induce d by i.c.v. MK-801 was evaluated in an effort to identify responses that ar e common to amphetamine and MK-801 and similarly augmented by food restrict ion. Unlike amphetamine, MK-801 did not increase FLI in caudate-putamen, be d nucleus of the stria terminalis, or ventral pallidum. Similar to amphetam ine, MK-801 increased FLI in cingulate cortex, central nucleus of the amygd ala and nucleus accumbens (NAC) core, but in none of these areas was the re sponse augmented by food restriction. In medial prefrontal cortex, retrospl enial cortex, and NAC shell, however, MK-801 induced FLI that was augmented by food restriction. An effect that is common to amphetamine and MK-801 is the augmentation of FLI by food restriction in NAC shell. It is therefore suggested that increased releasability of DA, or upregulation of the D-1 re ceptor linked signal transduction pathway, in NAC shell may mediate the enh anced behavioral sensitivity of food-restricted subjects to drugs of abuse. (C) 2000 Elsevier Science B.V. All rights reserved.