Dissociation of primary and secondary reward-relevant limbic nuclei in an animal model of relapse

Neuropsychopharmacology. 2000 May;22(5):473-9. doi: 10.1016/S0893-133X(99)00157-8.


The neural substrates underlying relapse to drug-seeking behavior after chronic drug abuse may differ from those underlying immediate drug-taking behavior. In a model of relapse to drug-seeking behavior following chronic cocaine self-administration and prolonged extinction, we have previously shown that rats will significantly reinstate lever responding for either primary reward (cocaine) or secondary reward (tone + light stimulus previously paired with cocaine). In the present study, we utilized reversible inactivation of discrete brain nuclei with tetrodotoxin (TTX) in order to examine the neural substrates mediating primary and secondary cocaine reward in rats allowed two weeks of cocaine self-administration. After one week of daily extinction sessions, bilateral inactivation of the basolateral amygdala resulted in significant attenuation of lever pressing for a cocaine-conditioned reward (tone + light). Following three more days of extinction, bilateral TTX inactivation of the basolateral amygdala had no effect on the reinstatement of cocaine self-administration. In contrast, TTX inactivation of the nucleus accumbens produced the exact opposite effects, with significant blockade of primary reward (cocaine alone), but not secondary reward (tone + light). Thus, cocaine-conditioned reward is neuroanatomically dissociated from primary cocaine reward.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amygdala / cytology
  • Amygdala / drug effects
  • Amygdala / physiopathology
  • Animals
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / physiopathology*
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors / pharmacology
  • Infusion Pumps, Implantable
  • Limbic System / cytology
  • Limbic System / drug effects*
  • Limbic System / physiopathology*
  • Male
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Recurrence
  • Reward*
  • Self Administration
  • Sodium Channels / drug effects
  • Tetrodotoxin / pharmacology


  • Dopamine Uptake Inhibitors
  • Sodium Channels
  • Tetrodotoxin
  • Cocaine