Review
Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning

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Abstract

The nucleus accumbens is a brain region that participates in the control of behaviors related to natural reinforcers, such as ingestion, sexual behavior, incentive and instrumental learning, and that also plays a role in addictive processes. This paper comprises a review of work from our laboratory that focuses on two main research areas: (i) the role of the nucleus accumbens in food motivation, and (ii) its putative functions in cellular plasticity underlying appetitive learning. First, work within a number of different behavioral paradigms has shown that accumbens neurochemical systems play specific and dissociable roles in different aspects of food seeking and food intake, and part of this function depends on integration with the lateral hypothalamus and amygdala. We propose that the nucleus accumbens integrates information related to cognitive, sensory, and emotional processing with hypothalamic mechanisms mediating energy balance. This system as a whole enables complex hierarchical control of adaptive ingestive behavior. Regarding the second research area, our studies examining acquisition of lever-pressing for food in rats have shown that activation of glutamate N-methyl-d-aspartate (NMDA) receptors, within broadly distributed but interconnected regions (nucleus accumbens core, posterior striatum, prefrontal cortex, basolateral and central amygdala), is critical for such learning to occur. This receptor stimulation triggers intracellular cascades that involve protein phosphorylation and new protein synthesis. It is hypothesized that activity in this distributed network (including D1 receptor activity) computes coincident events and thus enhances the probability that temporally related actions and events (e.g. lever pressing and delivery of reward) become associated. Such basic mechanisms of plasticity within this reinforcement learning network also appear to be profoundly affected in addiction.

Introduction

In recent years a great deal of progress has been made in advancing our understanding of the neural mechanisms underlying reward and motivation. Much of this knowledge has arisen from research funded by the National Institute on Drug Abuse (NIDA). The primary mission of NIDA within the context of its neurobiology research program has traditionally focused on mechanisms underlying the neurochemical and behavioral effects of drugs and addiction. However, NIDA has also emphasized that knowledge of the basic processes controlling appetitive motivation and natural reward processes (such as those regulating ingestive and sexual behaviors) can provide critical insights into the addiction process. Roger Brown, my program director for many years at NIDA, was a strong supporter of this philosophy and was always very supportive of our research, which mainly focuses on neural systems involving natural reward processing and learning, rather than directly addressing mechanisms of addiction. In the present review I will highlight several of the major areas of research that our laboratory has undertaken, funded by NIDA, over the past decade or so. It should be emphasized that this paper, which was presented at a special symposium honoring the life and work of Roger Brown, is not a comprehensive overview of these fields but rather focuses specifically on our own NIDA-funded research, in line with the spirit of the symposium.

Section snippets

The nucleus accumbens: functional specialization of subregions

The nucleus accumbens, a brain region located within the ventral aspects of the basal ganglia, has long been conceptualized as an essential interface between ‘motivation and action’. Mogenson first proposed this forebrain structure as a key element in the integration of affective and cognitive processing with voluntary motor actions [1]. He emphasized the connectivity of the nucleus accumbens, in that it received a convergence of information from brain regions involved in emotional learning,

Connectivity related to control of food intake

The nucleus accumbens is well positioned to participate in neural control of food intake. It is useful to examine how internal and external food- or appetite-related information gains access to this structure, and how it can influence output effector pathways controlling feeding (Fig. 1). First, the accumbens receives brainstem information related to taste and visceral functions through a direct input from the nucleus of the solitary tract (NTS; to the medial shell), as well as an indirect

Neurons within the nucleus accumbens core are critical for plasticity related to motor learning

A second broad area of our research has focused on the role of the nucleus accumbens and its connected circuitry in appetitive instrumental learning. These experiments derived from earlier findings implicated the core subregion of accumbens in exploration and learning [55], [56]. We have found, as discussed in detailed below, that glutamate, dopamine, and their respective receptors of the NMDA type and dopamine D1 type play a key role in initiating intracellular plasticity underlying adaptive

Conclusions

The above account summarizes the work of this laboratory over the past decade or so, which has helped to elucidate the functions of the nucleus accumbens and its related circuitry in reward-related behavior. Work with a number of different behavioral paradigms has shown that accumbens neurochemical systems play specific and differentiable roles in different aspects of food seeking and food intake, and part of this function depends on integration with amygdala and lateral hypothalamus. We

Acknowledgements

The work discussed in this review has been supported by grants DA09311 and DA04788 from the National Institute on Drug Abuse.

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