Double dissociation of the dorsomedial and dorsolateral striatal control over the acquisition and performance of cocaine seeking

Neuropsychopharmacology. 2012 Oct;37(11):2456-66. doi: 10.1038/npp.2012.104. Epub 2012 Jun 27.


The present study investigated the involvement of dopamine-dependent mechanisms in the anterior dorsolateral (aDLS) and posterior dorsomedial (pDMS) striatum during the early- and late-stage performance of cocaine-seeking behavior. Rats were trained to self-administer cocaine under continuous reinforcement (fixed-ratio 1, FR1) with a 20-s light conditioned stimulus (CS) presented contingently upon each infusion. After a week, rats were challenged by a change in contingency to seek cocaine during a 15-min period uninfluenced by cocaine during which each response was reinforced by a 1-s CS presentation. Dopamine transmission blockade by intracranial infusions of α-flupenthixol only in the pDMS, but not in the aDLS, dose dependently reduced performance of cue-controlled cocaine seeking at the early stage of self-administration. One cohort of rats was then trained with increasing response requirements until completing 15 sessions under a second-order schedule [FI15(FR10:S)] so that cocaine-seeking performance became well established. At this stage, intra-aDLS, but not pDMS, α-flupenthixol infusions dose dependently reduced active lever presses. The second cohort of rats continued to self-administer cocaine under the FR1 schedule such that their drug intake was matched to the late-stage performance group. α-Flupenthixol in the pDMS, but not in the aDLS, again prevented the performance of cocaine seeking. These results show that dopamine transmission in the pDMS is required for initial performance of goal-directed cocaine seeking, and that its role is ultimately subverted and devolves instead to the aDLS only following training with high rates of cocaine-seeking behavior, supporting the theory of dynamic shifts in the striatal control over cocaine seeking between goal-directed and habitual performance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects*
  • Corpus Striatum / anatomy & histology
  • Corpus Striatum / drug effects*
  • Corpus Striatum / physiology
  • Disease Models, Animal
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Flupenthixol / pharmacology
  • Male
  • Rats
  • Reinforcement Schedule
  • Reinforcement, Psychology
  • Self Administration


  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Flupenthixol
  • Cocaine