Year: 2016
Type: dissertation
Abstract: So far, investigations into the neural basis of affect have revealed discrete, anatomically localized sites called hedonic “hotspots” in nucleus accumbens (NAc) and ventral pallidum (VP) that are able to modulate the hedonic impact of a reward. Here, I further examined the localization and neurochemical specificity of the hotspots, as well as explored new potential sites of interest to more clearly establish a hedonic circuit. In Chapter 2, I focused on the NAc hotspot, testing the effects of mu, delta, or kappa opioid receptor stimulation on hedonic and motivated behaviors. I found that while all three opioid receptor subtypes could reliably enhance hedonic ‘liking’ in the hotspot, they all had unique effects on motivated food intake. In Chapter 3, I extended the neurochemical investigation to include orexin and acetylcholine systems within NAc. I found that like the opioids, orexin stimulations only enhanced hedonic impact in the rostral hotspot, but enhanced food intake throughout shell. By contrast, blockade of acetylcholine muscarinic receptors caused a broad shift toward ‘disgust’, reducing appetitive behaviors and enhancing aversive ones. In Chapter 4, I sought to determine whether any cortical sites were capable of modulating hedonic impact or motivation, especially orbitofrontal cortex (OFC) and insula. I found that both of these areas contained localized hedonic hotspots that were sensitive to mu or orexin stimulations. The OFC hotspot was localized to the rostral 2/3 of OFC, and the insula hotspot was localized to the far caudal 1/3. I also found a single large hedonic coldspot that started in caudolateral OFC and extended into anterior and mid insula. Lastly, in Chapter 4, I found that selectively stimulation of lateral hypothalamic inputs into the VP hotspot could enhance hedonic ‘liking’ reactions to sucrose, as well as intake of palatable M&Ms. By contrast, local VP stimulation only increased hedonic ‘liking’ reactions, and local LH stimulation only increased food intake. Collectively, these experiments expand the neurochemical repertoire of the hotspots, as well as expand the hedonic circuit to include cortical and hypothalamic mechanisms for generating affect, carrying important implications for the treatment of affective disorders like depression or bipolar.
Author: Castro, Daniel
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2580125165