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 rewarding effects that are mediated by a combination of dopamine-dependent and -independent mechanisms. It was recently demonstrated that, similar to amphetamine, the rewarding and locomotor effects of intraventricular (i.c.v.) MK-801 are potentiated by chronic food restriction. Because food restriction also increases c-Fos expression induced by i.c.v. amphetamine in several subcortical dopamine (DA) terminal areas, Fos-like immunoreactivity (FLI) induced by i.c.v. MK-801 was evaluated in an effort to identify responses that are common to amphetamine and MK-801 and similarly augmented by food restriction. Unlike amphetamine, MK-801 did not increase FLI in caudate-putamen, bed nucleus of the stria terminalis, or ventral pallidum. Similar to amphetamine, MK-801 increased FLI in cingulate cortex, central nucleus of the amygdala and nucleus accumbens (NAC) core, but in none of these areas was the response augmented by food restriction. In medial prefrontal cortex, retrosplenial 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 receptor linked signal transduction pathway, in NAC shell may mediate the enhanced behavioral sensitivity of food-restricted subjects to drugs of abuse.
Millhauser Laboratories, Department of Psychiatry, New York University, School of Medicine, 550 First Avenue, New York, NY 1 0016, USA. kc16@is4.nyu.edu
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D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005508:Food Deprivation / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000662:Amphetamines; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D016291:Dizocilpine Maleate