Neural correlates of inflexible behavior in the orbitofrontal-amygdalar circuit after cocaine exposure

Ann N Y Acad Sci. 2007 Dec:1121:598-609. doi: 10.1196/annals.1401.014. Epub 2007 Sep 10.

Abstract

Addiction is characterized by compulsive or inflexible behavior, observed both in the context of drug-seeking and in contexts unrelated to drugs. One possible contributor to these inflexible behaviors may be drug-induced dysfunction within circuits that support behavioral flexibility, including the basolateral amygdala (ABL) and the orbitofrontal cortex (OFC). Here we describe data demonstrating that chronic cocaine exposure causes long-lasting changes in encoding properties in the ABL and the OFC during learning and reversal in an odor-guided task. In particular, these data suggest that inflexible encoding in ABL neurons may be the proximal cause of cocaine-induced behavioral inflexibility, and that a loss of outcome-expectant encoding in OFC neurons could be a more distal contributor to this impairment. A similar mechanism of drug-induced orbitofrontal-amygdalar dysfunction may cause inflexible behavior when animals and addicts are exposed to drug-associated cues and contexts.

MeSH terms

  • Amygdala / drug effects*
  • Animals
  • Behavior / drug effects*
  • Behavior, Animal / drug effects*
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / pathology
  • Cocaine-Related Disorders / physiopathology
  • Decision Making / drug effects
  • Frontal Lobe / drug effects*
  • Humans
  • Neurons / drug effects*

Substances

  • Cocaine