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bioRxiv · 10.1101/2024.11.04.621937

Nucleus accumbens D2-expressing neurons: Balancing reward and licking disruption through rhythmic optogenetic stimulation

Requejo-Mendoza, N.·Arias-Montano, J.-A.·Gutierrez, R.
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Abstract

Dopamine D1 receptor-expressing neurons in the nucleus accumbens (NAc) are known to be critical for processing reward and regulating food intake. However, the role of D2-expressing neurons in this region remains less understood. This study employed optogenetic manipulations to investigate the role of NAc D2-expressing neurons in reward processing and sucrose consumption. Optogenetic activation of these neurons decreased sucrose preference (at 20 Hz), disrupted licking patterns (particularly at 8 and 20 Hz), and increased self-stimulation. Conversely, synchronizing stimulation with the animals licking rhythm mitigated licking disruption and even increased sucrose intake, suggesting a rewarding effect. Furthermore, 20 Hz stimulation (but not 8 Hz) induced place preference in a real-time place preference (RTPP) test. In contrast, inhibiting D2 neurons produced a negative hedonic state, although not reaching a complete aversion, influencing food choices in specific contexts. For instance, while the RTPP test per se was not sensitive enough to observe place aversion when mice could choose between consuming a high-fat diet (HFD) pellet in a context associated with or without inhibition of D2 neurons, they preferred to consume HFD on the non-inhibited side. This suggests that the palatability of HFD can unmask (but also overshadow) the negative hedonic state associated with D2 neuron inhibition. A negative reinforcement paradigm further confirmed the active avoidance behavior induced by D2 neuron inhibition. In conclusion, NAc D2 neuron inhibition induces a negative hedonic state, while activation has a dual effect--it is rewarding yet disrupts licking behavior--highlighting its complex role in reward and consummatory behavior. Importantly, self-paced stimulation, where the animal controls the timing of the stimulation by its licking behavior, offers a more efficient and natural approach for stimulating NAc activity.

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Requejo-Mendoza, N., Arias-Montano, J.-A., Gutierrez, R.. 2024-11-04. Nucleus accumbens D2-expressing neurons: Balancing reward and licking disruption through rhythmic optogenetic stimulation. https://doi.org/10.1101/2024.11.04.621937

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