Dissociable Mesocorticolimbic Contributions to Pleasure and Motivation
Morales, Ileana
2024
Abstract
Mesocorticolimbic systems are heavily implicated in the control of reward. Reward contains multiple components that include ‘liking’, ‘wanting’, and learning processes (Berridge, 2004; Berridge & Robinson, 2003; Morales & Berridge, 2020).Over many decades, most attention has been paid to understanding ‘wanting’ and learning components, and ‘liking’ has remained the least understood. However, recent progress in understanding brain generators of hedonic impact has been made through the identification of brain hedonic hotspots, or small subregions of mesocorticolimbic systems that causally amplify affective ‘liking’ expressions to pleasant tastes in nucleus accumbens medial shell (NAc), caudolateral ventral pallidum (VP), rostromedial orbitofrontal cortex (OFC), and caudal insula in response to a few neurochemical signals including orexin and mu-opioid receptor agonists (Castro et al., 2016; Castro & Berridge, 2014c, 2017; Ho & Berridge, 2013; Mahler et al., 2007; Peciña & Berridge, 2005; K. S. Smith & Berridge, 2005; Söderpalm & Berridge, 2000). Thus far, hedonic hotspot sites within mesocorticolimbic regions have primarily been studied using drug microinjection techniques, such as through the use of mu-opioid, orexin, and endocannabinoid agonists. This leaves open the possibility that hedonic hotspot amplification of ‘liking’ reactions is a mere artifact of the pharmacological approaches used, rather than a true neurobiological mechanism that exerts hedonic control. In order to provide triangulating evidence that hedonic hotspots are true neurofunctional entities capable of controlling affective responses, I use optogenetic techniques as an alternative method of controlling neuronal activity within known hedonic hotspot sites in OFC and insula in Chapter 2. In Chapter 3 I investigate a region of mid cingulate cortex in rats that has never been previously tested for hedonic function. In Chapter 4, my efforts move subcortically to probe the necessity of the caudolateral ventral pallidum hedonic hotspot for normal ‘liking’. Finally, in Chapter 5 I investigate amygdala control of incentive motivation for intravenous opioids. Altogether, this dissertation demonstrates that mesocorticolimbic systems in OFC, insula, cingulate cortex, ventral pallidum, and central amygdala are crucial sites for the control of ‘liking’ and/or ‘wanting’ for reward. Importantly however, ‘liking’ is restricted to small subregions of hedonic hotspots where optogenetic manipulations casually amplify hedonic impact for sweetness. Outside of these hotspots, optogenetic manipulations fail to increase ‘liking’ reactions, and sometimes even oppositely suppress affective reactions. In some cases, such in central amygdala, maladaptive ‘wanting’ can be generated for natural and drug rewards that is never matched in changes in ‘liking’. The neural mechanisms underlying these different motivational and hedonic processes provide important insights onto hedonic and motivational dysfunctions that may contribute to various affective and other psychological disorders.Deep Blue DOI
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Reward Motivation Affect
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