Stimulant-induced adaptations in neostriatal matrix and striosome systems: transiting from instrumental responding to habitual behavior in drug addiction

Neurobiol Learn Mem. 2005 Mar;83(2):93-103. doi: 10.1016/j.nlm.2004.10.006.


Converging evidence indicates that repeated exposure to motor stimulants such as cocaine and amphetamine produces marked alterations in network responsiveness of striatal neurons to subsequent challenge with the same stimulant drug. Such alterations, which correlate with persistent patterns of repetitive behavior, associate with distinct compartmental changes in the neostriatum. Striatal matrix system neurons undergo "silencing" following repeated drug challenges, allowing striosome system neurons to exhibit preferential activation. Matrix neurons are innervated by sensory and motor areas of neocortex and are activated in the course of on-going, adaptive behavior. Inactivation of matrix neurons by chronic stimulant exposure may therefore constrain sensorimotor and cognitive processing. In turn, the striosomes are anatomically connected through re-entrant loops with limbic prefrontal and allocortical structures, such as anterior cingulate cortex, orbital frontal cortex, and basolateral amygdala, all of which play a part in stimulant-induced reinforcement and relapse to drug-taking. Moreover, functional evidence links striosome system neurons, which are responsible for providing inhibitory regulatory feedback to midbrain dopamine neurons, with reinforcement-based processes. In considering such evidence, we postulate that recurrent matrix inactivation and recruitment of striosome-based pathways by chronic stimulant exposure represent neural end-points of the transit from action-outcome associative behavior to conditioned habitual responding. Within this theoretical framework, habitual behavior can be elicited by both interoceptive cues and exteroceptive conditioned stimuli to promote the automatic execution of learned responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphetamine / pharmacology*
  • Amphetamine-Related Disorders / physiopathology*
  • Animals
  • Arousal / drug effects*
  • Arousal / physiology
  • Basal Ganglia / drug effects
  • Basal Ganglia / physiopathology
  • Central Nervous System Stimulants / pharmacology*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiopathology
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / physiopathology*
  • Conditioning, Operant / drug effects*
  • Conditioning, Operant / physiology
  • Habituation, Psychophysiologic / drug effects*
  • Habituation, Psychophysiologic / physiology
  • Humans
  • Limbic System / drug effects
  • Limbic System / physiopathology
  • Neostriatum / drug effects*
  • Neostriatum / physiopathology
  • Nerve Net / drug effects*
  • Nerve Net / physiopathology
  • Neurons / drug effects
  • Neurons / physiology
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / physiology


  • Central Nervous System Stimulants
  • Receptors, Dopamine
  • Amphetamine
  • Cocaine