Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior

Psychopharmacology (Berl). 2001 Mar;154(3):301-10. doi: 10.1007/s002130000636.


Rationale: Following chronic cocaine self-administration and extinction, lesions of the basolateral amygdala (BLA) will significantly attenuate responding for secondary reward (tone + light previously paired with cocaine), without disrupting lever responding for primary reward. However, the specific neurotransmitters involved in conditioned reinstatement remain to be determined.

Objective: In the present study, we examined possible receptor substrates of amygdalar regulation of conditioned reinstatement after chronic cocaine self-administration.

Methods: Rats were allowed 2 weeks of 3-h daily sessions of cocaine self-administration along a fixed ratio (FR) 1 schedule. After 1 week of daily 3-h extinction sessions in which no programmed consequences occurred, selective antagonists of glutamate or dopamine (DA) receptors were bilaterally infused at single doses into the BLA prior to testing for a cocaine-conditioned reward (tone + light). Following three more days of extinction trials, receptor antagonist effects on reinstatement of cocaine self-administration in the absence of the conditioned stimulus were determined.

Results: Infusion of an NMDA receptor antagonist (AP-5, 1.97 micrograms/side), a kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (CNQX, 0.83 microgram/side), or both drugs together had no significant effects on conditioned reward or reinstatement of cocaine self-administration. In contrast, infusion of a DA D1 receptor antagonist (SCH-23390, 2 micrograms/side) or a combination of SCH-23390 and a DA D2/D3 receptor antagonist (raclopride, 5 micrograms/side) significantly reduced responding for conditioned reward, but did not affect cocaine self-administration. Raclopride alone was without effect on either test day.

Conclusions: These results suggest that conditioned reinstatement of drug-seeking behavior is dependent on amygdalar D1 receptors.

Publication types

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

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Amygdala / drug effects*
  • Amygdala / physiology
  • Animals
  • Behavior, Addictive / psychology
  • Benzazepines / pharmacology
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Conditioning, Operant / physiology
  • Dopamine Antagonists / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Raclopride / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Receptors, Dopamine D1 / physiology
  • Recurrence
  • Reward
  • Self Administration / psychology


  • Benzazepines
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Antagonists
  • Receptors, Dopamine D1
  • Raclopride
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Cocaine