Abstract
Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.
Highlights
Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion
To verify that the nucleus accumbens (NAc) was critically recruited in motivationdependent tasks, we evaluated the neuronal activation pattern of different brain regions after the Pavlovian-to-Instrumental transfer (PIT) and the Progressive-Ratio tasks (PR)
Recent findings show that phasic dopamine release drives a rapid activation of D2 MSNs34, suggesting that some of the behavioural effects of phasic release may be partially mediated by D2 signalling
Summary
Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. D1-MSN activation is canonically related to positive rewarding events, inducing persistent reinforcement, whereas D2-MSN signalling is thought to mediate aversion (both in dorsal striatum and NAc)[10,11,12]. Recent studies raised some questions regarding this functional/behavioural bias, especially regarding D2 neurons in the NAc13–15. Taking this into consideration, we used an optogenetic approach to address the impact of modulating NAc D1 and D2 neurons in motivation-dependent behaviours
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