Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats

Psychopharmacology (Berl). 2002 Apr;160(4):425-33. doi: 10.1007/s00213-001-0997-7. Epub 2002 Feb 14.


Rationale: Drug-paired stimuli elicit drug craving and relapse in addicts and drug-seeking behavior in rats. The functional integrity of the basolateral amygdala (BLA) is necessary for reinstatement of cocaine-seeking behavior elicited by cocaine-conditioned stimuli, but not by cocaine itself. It is unclear, however, whether the BLA plays a similar role in reinstatement of heroin-seeking behavior.

Objectives: To this end, we examined the effects of tetrodotoxin (TTX)-induced inactivation of the BLA on conditioned and heroin-primed reinstatement of extinguished heroin-seeking behavior.

Methods: Rats were trained to press a lever for IV infusions of heroin (maintenance dose of 25 microg/infusion) paired with presentations of a light-tone stimulus complex during daily 3-h sessions. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of extinguished heroin-seeking behavior (i.e. lever pressing in the absence of heroin reinforcement) was measured in the presence of response-contingent presentation of the heroin-paired stimulus complex alone and then following TTX (5 ng/0.5 microl per side) or vehicle infused into the BLA. In a separate group of rats, reinstatement was measured after saline injection (SC) and then following heroin priming (0.25 mg/kg, SC) with TTX or vehicle infused into the BLA.

Results: Both response contingent presentation of the stimulus complex and heroin priming significantly reinstated extinguished heroin-seeking behavior, and BLA inactivation abolished the ability of the heroin-paired stimuli and of heroin priming to reinstate responding.

Conclusions: These findings suggests that the BLA is a critical component of the neural circuitry that mediates conditioned and heroin-induced reinstatement of heroin-seeking behavior. Furthermore, different neural substrates may mediate drug-primed relapse to cocaine versus heroin-seeking behavior.

Publication types

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

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiology*
  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / pharmacology
  • Animals
  • Behavior, Addictive / physiopathology*
  • Behavior, Addictive / psychology
  • Catheterization
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology*
  • Heroin / administration & dosage
  • Heroin / pharmacology*
  • Injections, Intraventricular
  • Male
  • Narcotics / administration & dosage
  • Narcotics / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Self Administration
  • Tetrodotoxin / administration & dosage
  • Tetrodotoxin / pharmacology


  • Anesthetics, Local
  • Narcotics
  • Tetrodotoxin
  • Heroin