Orexin in Rostral Hotspot of Nucleus Accumbens Enhances Sucrose ‘Liking’ and Intake but Scopolamine in Caudal Shell Shifts ‘Liking’ Toward ‘Disgust’ and ‘Fear’

Abstract

The nucleus accumbens (NAc) contains a hedonic hotspot in the rostral half of medial shell, where opioid agonist microinjections are known to enhance positive hedonic orofacial reactions to the taste of sucrose ('liking' reactions). Within NAc shell, orexin/hypocretin also has been reported to stimulate food intake and is implicated in reward, whereas blockade of muscarinic acetylcholine receptors by scopolamine suppresses intake and may have anti-reward effects. Here, we show that NAc microinjection of orexin-A in medial shell amplifies the hedonic impact of sucrose taste, but only within the same anatomically rostral site, identical to the opioid hotspot. By comparison, at all sites throughout medial shell, orexin microinjections stimulated 'wanting' to eat, as reflected by increases in intake of palatable sweet chocolates. At NAc shell sites outside the hotspot, orexin selectively enhanced 'wanting' to eat without enhancing sweetness 'liking' reactions. In contrast, microinjections of the antagonist scopolamine at all sites in NAc shell suppressed sucrose 'liking' reactions as well as suppressing intake of palatable food. Conversely, scopolamine increased aversive 'disgust' reactions elicited by bitter quinine at all NAc shell sites. Finally, scopolamine microinjections localized to the caudal half of medial shell additionally generated a fearrelated anti-predator reaction of defensive treading and burying directed toward the corners of the transparent chamber. Together, these results confirm a rostral hotspot in NAc medial shell as a unique site for orexin induction of hedonic 'liking' enhancement, similar to opioid enhancement. They also reveal distinct roles for orexin and acetylcholine signals in NAc shell for hedonic reactions and motivated behaviors.

A Decade of Orexin/Hypocretin and Addiction: Where Are We Now?

“…The effects of intra-NAc infusions of orexin receptor agonists or antagonists have not been examined for psychostimulants, but local infusions of SB-334867 or TCS-29-029 in NAcSh prevent stress-induced reinstatement of morphine conditioned place preference [69], and injections of TCS-OX2-029 in NAcC reduced responding for ethanol [51]. Also, injections of orexin-A into the rostral half of medial NAcSh increase the hedonic “liking” for sucrose taste [138], as do orexin-A injections into the posterior half of the ventral pallidum [139]. …”

Orexin/Hypocretin System: Role in Food and Drug Overconsumption

“…Thus, OX-A increases the intake of M&Ms ® when injected into the nucleus accumbens shell (Castro, Terry, & Berridge, 2016), of a sucrose solution and high-fat diet after injection into the ventral tegmental area (Terrill et al, 2016), and of a sucrose solution after injection into the paraventricular thalamus (Barson, Ho, & Leibowitz, 2015). Conversely, the OX1R antagonist SB-334867 reduces drinking of sucrose when injected into the ventral tegmental area (Terrill et al, 2016), and knockdown of the OX1R in the paraventricular thalamus suppresses the consumption of a high-fat diet (Choi et al, 2012).…”

Multimodal connectivity‐based parcellation reveals a shell‐core dichotomy of the human nucleus accumbens

“…Functionally, the core plays a role in selectively instigating an approach toward an incentive stimulus associated with the best available reward after Pavlovian cue encoding. In addition, more accurate, anatomically localized studies suggested that the NAc shell and core play prominent roles in reward [Castro and Berridge, 2014;Pecina and Berridge, 2005] and aversion [Castro et al, 2016;Yamaguchi et al, 2015] processing, respectively. DBS of the NAc shell and core also resulted in opposite effects on impulsive action [Sesia et al, 2008].…”