Hedonic hotspot in rat olfactory tubercle: map for mu-opioid, orexin, and muscimol enhancement of sucrose ‘liking’

Pleasure plays a crucial role in positive reinforcement and motivation. Brain regions able to amplify positive hedonic reactions to sweetness, known as ‘hedonic hotspots’, are distributed within the mesocorticolimbic reward systems. The olfactory tubercle (OT), a part of the ventral striatum that receives olfactory input, contains distinct functional domains: the anteromedial domain mediates approach motivation toward odors associated with food, whereas the lateral domain mediates avoidance motivation away from odors associated with danger. However, it has remained unclear whether the OT modulates hedonic reactions to pleasant sensations. In this study, we made pharmacological microinjections in OT of in rats to examine whether these OT subregions can modulate hedonic reactions, as assessed by the taste reactivity test. Sweet oral infusions of sucrose solution were delivered into the mouth via an intraoral cannula, and the rats’ orofacial and somatic hedonic reactions were recorded and analyzed. We compared three pharmacological agents: mu-opioid receptor agonist DAMGO, orexin-A peptide, and GABA _A receptor agonist muscimol. Microinjection of any of these drugs into the anteromedial OT subregion enhanced hedonic ‘liking’ reactions to sucrose. Furthermore, DAMGO injection into the anteromedial OT subregion recruited distant Fos expression in other ‘hedonic hotspots’, including in the caudal ventral pallidum and the rostromedial orbitofrontal cortex. By contrast, the same microinjections into the anterolateral OT subregion failed to enhance ‘liking’ reactions and, DAMGO oppositely increased aversive ‘disgust’ reactions. These findings suggest that the anteromedial OT contains a ‘hedonic hotspot’, whereas the anterolateral OT may contain a suppressive opioid ‘hedonic coldspot’. Thus, OT subregions may help causally modulate hedonic reactions to sweetness and flavor perception.