Chronic food restriction increases Fos-like immunoreactivity (FLI) inducedin rat forebrain by intraventricular amphetamine

Chronic food restriction enhances behavioral responsiveness to amphetamine and other abused drugs. Because this effect is evident when drugs are admin istered intracerebroventricularly (i.c.v.) as well as systemically, it woul d seem to reflect increased sensitivity of a neural substrate rather than a change in drug disposition. In the present study, c-Fos immunohistochemist ry was used to evaluate whether the magnitude and pattern of cellular activ ation induced by i.c.v, amphetamine is altered by a regimen of food restric tion previously shown to potentiate amphetamine reward. In the absence of a mphetamine challenge, there was generally no difference in brain Fos-like i mmunoreactivity (FLI) between ad libitum fed and food-restricted mts. In re sponse to amphetamine (50 mu g), both groups displayed increased FLI in cau date-putamen, nucleus accumbens, bed nucleus of the stria terminalis, ventr al pallidum, central nucleus of the amygdala, and cingulate cortex. With th e exception of cingulate cortex and caudal caudate-putamen, a significantly greater response was observed in brain regions of food-restricted rats. Th ese results indicate that food restriction augments a cellular immediate ea rly gene (LEG) response to acute amphetamine in brain regions known to medi ate rewarding and other behavioral effects of psychostimulants. The differe nce between these results and those produced by sensitizing regimens of psy chostimulant exposure are discussed, as are possible endocrine factors that could be involved in the modulatory effect of food restriction on cellular and behavioral responses to amphetamine. (C) 2000 Published by Elsevier Sc ience B.V. All rights reserved.