A dopamine-dependent signal in the nucleus accumbens invigorates reward- seeking behavior
du Hoffmann, Johann Faustus
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Decades of research have implicated ventral striatal dopamine in conditioned appetitive behaviors. We began with the observation that if the ventral striatal dopamine signal is impaired so is the ability of experimental subjects to approach reward-associated goals. A large population of ventral striatal neurons exhibits excitation elicited by reward-predictive cues. Intriguingly, the magnitude of these excitations predicts the presence (or absence) of subsequent reward-seeking behavior. We hypothesized that ventral striatal cue-evoked excitation is facilitated by dopamine and that this is the neural substrate that mediates conditioned approach to reward-associated objects. However, there was no experimental method available to test this hypothesis. To overcome this limitation, we developed a novel approach that enables us to record from neurons and locally infuse pharmacological agents in the same brain nucleus of behaving rats. We extensively tested this system and demonstrated that this method facilitates highly predictable, replicable and quantifiable drug effects on recorded neurons. Next, we locally infused dopamine receptor antagonists while recording from ensembles of neurons in ventral striatum as trained rats responded to reward predictive cues. In this manner, we directly tested the standard model of basal ganglia function which predicts that dopamine has both excitatory and inhibitory effects on neurons mediated by activation of D 1-like and D2-like dopamine receptors, respectively. We show that the net effect of signaling through either dopamine receptor type is to facilitate excitation, not inhibition. We demonstrate that co-activation of both dopamine receptor families specifically contributes to cue-evoked excitation and that this is required for environmentally cued appetitive behavior. Additionally, we show that tonic activation of dopamine receptors by agonists promotes cued approach behavior and antagonists to the same receptors have the opposite effect. This bidirectional control of appetitive behavior by pharmacological modulation of ventral striatal dopamine signaling firmly establishes its important role in cued approach behavior. In conclusion, we demonstrate the neural mechanism by which ventral striatal dopamine promotes reward-seeking: dopamine facilitates vigorous short latency approach behavior by facilitating strong cue-evoked excitation in ventral striatum.
- Theses and Dissertations