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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology
  • Craving
  • Drug-Seeking Behavior
  • Extinction, Psychological
  • Male
  • Motivation*
  • Neurons*
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / physiopathology*
  • Optogenetics
  • Rats
  • Rats, Long-Evans
  • Self Administration
  • Space Perception