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Neuron. 2019 Jul 3;103(1):80-91.e7. doi: 10.1016/j.neuron.2019.04.015. Epub 2019 May 14.

Increased Cocaine Motivation Is Associated with Degraded Spatial and Temporal Representations in IL-NAc Neurons.

Author information

1
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA.
2
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA.
3
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA. Electronic address: iwitten@princeton.edu.

Abstract

Craving for cocaine progressively increases in cocaine users during drug-free periods, contributing to relapse. The projection from the infralimbic cortex to the nucleus accumbens shell (IL-NAc) is thought to inhibit cocaine seeking. However, it is not known whether and how IL-NAc neurons contribute to the increased motivation associated with a drug-free period. We first performed cellular resolution imaging of IL-NAc neurons in rats during a drug-seeking test. This revealed neurons with spatial selectivity within the cocaine-associated context, a decrease in activity around the time of cocaine seeking, and an inverse relationship between cocaine-seeking activity and subsequent cocaine motivation. All these properties were reduced by a drug-free period. Next, we transiently activated this projection, which resulted in reduced drug seeking, regardless of the drug-free period. Taken together, this suggests that altered IL-NAc activity after a drug-free period may enhance cocaine motivation without fundamentally altering the projection's ability to inhibit drug seeking.

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