Enhanced intake of high-fat food following striatal mu-opioid stimulation:Microinjection mapping and Fos expression

Our previous studies have shown that stimulation of mu-opioid receptors wit hin the nucleus accumbens preferentially enhances intake of palatable food containing sucrose and fat; thus, opioids in this brain area may mediate th e rewarding characteristics of food by modulating taste and macronutrient p reference. The present study was designed to further explore the nature of the involvement of striatal opioids in feeding behavior, such as the locati on of sensitive subregions of the ventral striatum and the brain neural cir cuits involved in opioid-mediated hyperphagia. In Experiment 1, we conducte d a microinfusion mapping study of feeding behavior by microinfusion of the mu receptor agonist, D-Ala(2),NMe-Phe(4),Glyol(5)-enkephalin (0, 0.025 and 0.25 mu g/0.5 mu l per side; equivalent to 0, 0.04 and 0.40 nmol/0.5 mu l per side), into several striatal subregions. In Experiment 2, detection of the expression of the immediate early gene, c-fos, was used to examine brai n areas activated following intra-striatal microinfusion of D-Ala(2),NMe-Ph e(4),Glyol(5)-enkephalin. The microinjection mapping study demonstrated a b road anatomical gradient within the striatum, with sensitivity highest in r elatively more lateral and ventral regions of the striatum (ventrolateral s triatum, lateral shell and core). The Fos mapping study demonstrated that c ircuitry including hypothalamic areas, the ventral tegmental area, the subs tantia nigra and the nucleus of the solitary tract was recruited by stimula tion of mu receptors within the nucleus accumbens. A similar pattern was ob served following stimulation of mu receptors in the dorsal striatum; howeve r, the extent of activation was much smaller in magnitude. These results suggest that the role of mu receptors within the striatum in palatable feeding primarily involves ventral and lateral regions. Moreover, the pattern of activation in hypothalamic, midbrain and gustatory-visceral relay areas suggests that striatal mu receptors may participate in integra ting motivational, metabolic and autonomic aspects of ingestive behavior. ( C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.