Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula

Abstract

Hedonic hotspots are brain sites where particular neurochemical stimulations causally amplify the hedonic impact of sensory rewards, such as "liking" for sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was found in posterior insula. A suppressive hedonic coldspot was also found in the form of an intervening strip stretching from the posterior OFC through the anterior and middle insula, bracketed by the two cortical hotspots. Opioid/orexin stimulations in either cortical hotspot activated Fos throughout a distributed "hedonic circuit" involving cortical and subcortical structures. Conversely, cortical coldspot stimulation activated circuitry for "hedonic suppression." Finally, food intake was increased by stimulations at several prefrontal cortical sites, indicating that the anatomical substrates in cortex for enhancing the motivation to eat are discriminable from those for hedonic impact.

Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus

“…The model postulates that besides positive emotional, cognitive and hedonic drivers, PF overeating results from a disruption of the ability of leptin to influence communication between Gal and OX neurons since activation of Gal2R in the LHA reduces PF consumption (see Figure 5C-E) | 11 of 16 LEIDMAA Et AL feeding behaviour, which is essential for survival, depends on in-built fail-safe mechanisms, rather than simple homeostatic reflexes. [58][59][60] Rather, it highlights input-output relationships between the LHA and periphery as well as brain areas that receive and process sensory information 4,43,61 ; among these, the central amygdala and VTA, both innervated by OX-ergic neurons in the LHA, contribute to flavour and reward learning. Thus, the hypophagic response to just a single hormone (eg leptin) may be small and probabilistic.…”

“…The model shown in Figure 7 is necessarily simple -it does not include all of the proposed molecular players and switches through which PF may modulate leptin signalling and actions in the hypothalamus. [58][59][60] Rather, it highlights input-output relationships between the LHA and periphery as well as brain areas that receive and process sensory information 4,43,61 ; among these, the central amygdala and VTA, both innervated by OX-ergic neurons in the LHA, contribute to flavour and reward learning. 4,62-66…”

Mu-opioids suppress GABAergic synaptic transmission onto orbitofrontal cortex pyramidal neurons with subregional selectivity

“…Given that mu-opioids elicit regionally distinct orofacial affective responses in the OFC (Castro and Berridge, 2017), and that they act predominantly via disinhibition to excite output neurons, we hypothesized that mu-opioids differentially modulate inhibitory synaptic transmission onto pyramidal neurons within the mOFC and lOFC. We first examined the effect of the selective mu-opioid receptor agonist, DAMGO (1 µM) on eIPSCs from layer II/III pyramidal neurons in the lOFC (Fig.…”

“…However, there is heterogeneity in this functional mu-opioid action depending on location within the OFC. In addition to a hedonic "hotspot" found in the anterior mOFC, there is an oppositely valenced "coldspot" in the posterior lOFC, such that muopioid application suppresses hedonic orofacial reactions to sucrose (Castro and Berridge, 2017). These anatomically distinct functional effects suggest there are sub-regional variations in mu-opioid receptor action across the OFC.…”

“…The mu-opioid receptor is abundantly expressed in the OFC (Mansour et al, 1995) and its signaling cascade is activated by the highly selective mu-opioid receptor peptide agonist, DAMGO. Microinjections of DAMGO into the OFC enhances both hedonic orofacial affective responses, as well as consumption of food rewards (Mucha and Iversen, 1986;Badiani et al, 1995;MacDonald et al, 2004;Mena et al, 2011;Castro and Berridge, 2017). However, there is heterogeneity in this functional mu-opioid action depending on location within the OFC.…”