Associative processes in addiction and reward - The role of amygdala-ventral striatal subsystems

Only recently have the functional implications of the organization of the ventral striatum, amygdala, and related limbic-cortical structures, and their neuroanatomical interactions begun to be clarified. Processes of activation and reward have long been associated with the NAcc and its dopamine innervation, but the precise relationships between these constructs have remained elusive. We have sought to enrich our understanding of the special role of the ventral striatum in coordinating the contribution of different functional subsystems to confer flexibility, as well as coherence and vigor, to goal-directed behavior, through different forms of associative learning. Such appetitive behavior comprises many subcomponents, some of which we have isolated in these experiments to reveal that, not surprisingly, the mechanisms by which an animal sequences responding to reach a goal are complex. The data reveal how the different components, pavlovian approach (or sign-tracking), conditioned reinforcement (whereby pavlovian stimuli control goal-directed action), and also more general response-invigorating processes (often called "activation," "stress," or "drive") may be integrated within the ventral striatum through convergent interactions of the amygdala, other limbic cortical structures, and the mesolimbic dopamine system to produce coherent behavior. The position is probably not far different when considering aversively motivated behavior. Although it may be necessary to employ simplified, even abstract, paradigms for isolating these mechanisms, their concerted action can readily be appreciated in an adaptive, functional setting, such as the responding by rats for intravenous cocaine under a second-order schedule of reinforcement. Here, the interactions of primary reinforcement, psychomotor activation, pavlovian conditioning, and the control that drug cues exert over the integrated drug-seeking response can be seen to operate both serially and concurrently. The power of our analytic techniques for understanding complex motivated behavior has been evident for some time. However, the crucial point is that we are now able to map these components with increasing certainty onto discrete amygdaloid, and other Limbic cortical-ventral striatal subsystems. The neural dissection of these mechanisms also serves an important theoretical purpose in helping to validate the various hypothetical constructs and further developing theory. Major challenges remain, not the least of which is an understanding of the operation of the ventral striatum together with its dopaminergic innervation and its interactions with the basolateral amygdala, hippocampal formation, and prefrontal cortex at a more mechanistic, neuronal level.