Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration

Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8750-E8759. doi: 10.1073/pnas.1707822114. Epub 2017 Sep 25.


The basolateral amygdala (BLA) sends excitatory projections to the nucleus accumbens (NAc) and regulates motivated behaviors partially by activating NAc medium spiny neurons (MSNs). Here, we characterized a feedforward inhibition circuit, through which BLA-evoked activation of NAc shell (NAcSh) MSNs was fine-tuned by GABAergic monosynaptic innervation from adjacent fast-spiking interneurons (FSIs). Specifically, BLA-to-NAcSh projections predominantly innervated NAcSh FSIs compared with MSNs and triggered action potentials in FSIs preceding BLA-mediated activation of MSNs. Due to these anatomical and temporal properties, activation of the BLA-to-NAcSh projection resulted in a rapid FSI-mediated inhibition of MSNs, timing-contingently dictating BLA-evoked activation of MSNs. Cocaine self-administration selectively and persistently up-regulated the presynaptic release probability of BLA-to-FSI synapses, entailing enhanced FSI-mediated feedforward inhibition of MSNs upon BLA activation. Experimentally enhancing the BLA-to-FSI transmission in vivo expedited the acquisition of cocaine self-administration. These results reveal a previously unidentified role of an FSI-embedded circuit in regulating NAc-based drug seeking and taking.

Keywords: basolateral amygdala; cocaine addiction; fast-spiking interneuron; medium spiny neuron; synaptic plasticity.

Publication types

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

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Basolateral Nuclear Complex
  • Cocaine / administration & dosage*
  • Drug-Seeking Behavior / physiology*
  • Female
  • Gene Knock-In Techniques
  • Long-Term Synaptic Depression
  • Male
  • Mice, Inbred C57BL
  • Neural Inhibition*
  • Neurons / cytology
  • Neurons / physiology*
  • Nucleus Accumbens / physiology*
  • Receptor, Cannabinoid, CB1 / physiology
  • Self Administration
  • Vasoconstrictor Agents / administration & dosage*


  • Receptor, Cannabinoid, CB1
  • Vasoconstrictor Agents
  • Cocaine