Optogenetic inhibition of cortical afferents in the nucleus accumbens simultaneously prevents cue-induced transient synaptic potentiation and cocaine-seeking behavior

Brain Struct Funct. 2016 Apr;221(3):1681-9. doi: 10.1007/s00429-015-0997-8. Epub 2015 Feb 7.


Animal models of relapse reveal that the motivation to seek drug is regulated by enduring morphological and physiological changes in the nucleus accumbens, as well as transient synaptic potentiation in the accumbens core (NAcore) that parallels drug-seeking behavior. The current study sought to examine the link between the behavioral and synaptic consequences of cue-induced cocaine seeking by optically silencing glutamatergic afferents to the NAcore from the prelimbic cortex (PL). Adeno-associated virus coding for the inhibitory opsin archaerhodopsin was microinjected into PL, and optical fibers were targeted to NAcore. Animals were trained to self-administer cocaine followed by extinction training, and then underwent cue-induced reinstatement in the presence or absence of 15 min of optically induced inhibition of PL fibers in NAcore. Inhibiting the PL-to-NAcore projection blocked reinstated behavior and was paralleled by decreased dendritic spine head diameter and AMPA/NMDA ratio relative to sham-laser control rats. Interestingly, while spine density was elevated after extinction training, no further effects were observed by cued reinstatement or optical inhibition. These findings validate the critical role for PL afferents to the NAcore in simultaneously regulating both reinstated behavior and the associated transient synaptic potentiation.

Keywords: Archaerhodopsin; Cocaine seeking; Dendritic spines; Nucleus accumbens; Optogenetic; Prelimbic prefrontal cortex; Reinstatement.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Afferent Pathways / cytology
  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology
  • Animals
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Cues
  • Dendritic Spines / drug effects
  • Drug-Seeking Behavior / physiology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Male
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / physiology*
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiology*
  • Optogenetics
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration


  • Cocaine