Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum

Neuron. 2008 Feb 7;57(3):432-41. doi: 10.1016/j.neuron.2007.12.019.


A neuroanatomical principle of striatal organization has been established through which ventral domains, including the nucleus accumbens, exert control over dorsal striatal processes mediated by so-called "spiraling," striato-nigro-striatal, circuitry. We have investigated the functional significance of this circuitry in the control over a cocaine-seeking habit by using an intrastriatal disconnection procedure that combined a selective, unilateral lesion of the nucleus accumbens core and infusion of a dopamine receptor antagonist into the contralateral dorsolateral striatum, thereby disrupting striato-midbrain-striatal serial connectivity bilaterally. We show that this disconnection selectively decreased drug-seeking behavior in rats extensively trained under a second-order schedule of cocaine reinforcement. These data thereby define the importance of interactions between ventral and dorsal domains of the striatum, mediated by dopaminergic transmission, in the neural mechanisms underlying the development and performance of cocaine-seeking habits that are a key characteristic of drug addiction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Addictive* / etiology
  • Behavior, Addictive* / pathology
  • Behavior, Addictive* / psychology
  • Behavior, Animal
  • Cocaine / adverse effects
  • Cocaine-Related Disorders / complications*
  • Cocaine-Related Disorders / etiology
  • Conditioning, Operant / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / adverse effects
  • Dose-Response Relationship, Drug
  • Flupenthixol / pharmacology
  • Male
  • Nerve Net / drug effects
  • Nerve Net / injuries
  • Nerve Net / pathology
  • Nerve Net / physiopathology*
  • Rats
  • Self Administration / methods


  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Flupenthixol
  • Cocaine
  • Dopamine