Renewal of extinguished cocaine-seeking

Neuroscience. 2008 Feb 6;151(3):659-70. doi: 10.1016/j.neuroscience.2007.11.018. Epub 2007 Nov 28.

Abstract

Rats were trained to self-administer cocaine in a distinctive context (context A). They were then extinguished in a second context (context B) prior to test for cocaine-seeking in the original training context, context A (group ABA), context B (group ABB) or no test (group AB0). Group ABA showed renewal of extinguished cocaine-seeking associated with c-Fos induction in basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Groups ABA and ABB showed test-associated c-Fos induction in prelimbic prefrontal cortex, nucleus accumbens (core, shell, rostral pole), striatum, lateral amygdala, perifornical hypothalamus, and ventral tegmental area. Double immunofluorescence revealed that renewal-associated c-Fos was expressed in orexin-negative lateral hypothalamic neurons whereas test-associated c-Fos was expressed in orexin-positive perifornical hypothalamic neurons. Retrograde tracing from lateral hypothalamus with cholera toxin revealed only sparse dual-labeled neurons in basolateral amygdala and infralimbic prefrontal cortex, suggesting that these regions contribute to renewal of cocaine-seeking independently of their projections to lateral hypothalamus. Retrograde tracing from the ventral tegmental area suggested that hypothalamic contributions to cocaine-seeking are likewise independent of projections to the midbrain. These results suggest that renewal of cocaine-seeking depends critically on basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Whereas basolateral amygdala and lateral hypothalamus contributions may be common to renewal of extinguished cocaine-, alcohol-, and sucrose-seeking, infralimbic prefrontal cortex contributions appear unique to renewal of cocaine-seeking and may reflect the habitual nature of relapse to cocaine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism
  • Brain Mapping
  • Cell Count / methods
  • Cholera Toxin / metabolism
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / etiology
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuropeptides / metabolism
  • Orexins
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Long-Evans
  • Self Administration
  • Time Factors

Substances

  • Dopamine Uptake Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Proto-Oncogene Proteins c-fos
  • Cholera Toxin
  • Cocaine