Hedonic Hot Spot in Nucleus Accumbens Shell: Where Do μ-Opioids Cause Increased Hedonic Impact of Sweetness?

Abstract

-Opioid systems in the medial shell of the nucleus accumbens contribute to hedonic impact ("liking") for sweetness, food, and drug rewards. But does the entire medial shell generate reward hedonic impact? Or is there a specific localized site for opioid enhancement of hedonic "liking" in the medial shell? And how does enhanced taste hedonic impact relate to opioid-stimulated increases in food intake? Here, we used a functional mapping procedure based on microinjection Fos plumes to localize opioid substrates in the medial shell of the nucleus accumbens that cause enhanced "liking" reactions to sweet pleasure and that stimulate food intake. We mapped changes in affective orofacial reactions of "liking"/"disliking" elicited by sucrose or quinine tastes after D-Ala 2 -N-Me-Phe 4 -Glycol 5-enkephalin (DAMGO) microinjections in rats and compared hedonic increases to food intake stimulated at the same sites. Our maps indicate that opioid-induced increases in sucrose hedonic impact are generated by a localized cubic millimeter site in a rostrodorsal region of the medial shell. In contrast, all regions of the medial shell generated DAMGO-induced robust increases in eating behavior and food intake. Thus, our results identify a locus for opioid amplification of hedonic impact and reveal a distinction between opioid mechanisms of food intake and hedonic impact. Opioid circuits for stimulating food intake are widely distributed, whereas hedonic "liking" circuits are more tightly localized in the rostromedial shell of the nucleus accumbens.

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

“…Because initial time-course results indicated that anandamide effects were maximal and constant 30-45 min after microinjection, rats in the comparison group received an oral infusion of 1% sucrose solution (1 ml volume, 1 min duration) at 30 min after drug, and received a second oral infusion of 3 Â 10 À4 M quinine (1 ml volume, 1 min duration) 15 min later at 45 min after the drug. This order of testing was used to ensure that 'liking' reactions to sucrose were always pure and uncontaminated by any prior taste on that day, because positive hedonic 'liking' reactions are generally more vulnerable to disruption than negative 'disliking' reactions, and because it is identical to the procedure used in a previous mapping study of the accumbens hedonic hotspot (Peciña and Berridge, 2005).…”

“…Fos densities were also measured around the site of anandamide microinjections to assess drug-induced elevations of local Fos expression (Figure 1). In this study, we improved the sensitivity of detection of elevated Fos expression, mapping 2 Â and 3 Â elevations over control levels in addition to higher levels, compared to previous studies that detected 45 Â as the lowest increase over control levels (Peciña and Berridge, 2005;Smith and Berridge, 2005).…”

“…Plume-sized hexagons matching the sizes of intense, moderate, and low Fos plumes were color-coded to reflect the quality and magnitude of behavioral effects produced by anandamide microinjection at that site, and plotted onto each corresponding site location (mapping figures represent anandamide plumes relative to lower, normal tissue baselines, to avoid underestimation of drug spread (Peciña and Berridge, 2005;Smith and Berridge, 2005). Anandamide increased hedonic reactions to sucrose at most microinjection sites, within approximately 2.75 mm 3 volume that extended over most of the medial shell.…”

“…For example, a 1 mm 3 'hedonic hotspot' was recently found in the medial shell where m opioid receptor activation by DAMGO microinjections tripled positive 'liking' orofacial reactions that are elicited by sucrose taste in rats (Peciña and Berridge, 2005), and stimulated food intake (though the intake 'wanting' site extended further) (Bakshi and Kelley, 1993;Zhang and Kelley, 2000;Peciña and Berridge, 2005). Opioid and endocannabinoid neurotransmissions are known to positively interact (Tanda et al, 1997;Kirkham and Williams, 2001;Navarro et al, 2001;Rowland et al, 2001;Williams and Kirkham, 2002b;Verty et al, 2003;Solinas and Goldberg, 2005;Vigano et al, 2005;Caille and Parsons, 2006;Cota et al, 2006), raising the possibility that endocannabinoid receptor activation might increase 'liking' for natural rewards in the same hedonic hotspot of the medial accumbens shell where opioids do so.…”

Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

“…For example, a 1 mm locus of the rat nucleus accumbens (NAc) shell has been implicated in responses to hedonic stimuli. 1 Chemical analysis and histochemical imaging of brain tissue have revealed distribution of neurotransmitters, 2,3 processing enzymes, 4,5 receptors, 6,7 and reuptake proteins 2,8,9 that presumably underlie functional heterogeneity in the brain. Although these approaches give an important view of brain organization, they do not provide distribution of neurotransmitters where they are actually active, that is, in the extracellular space.…”