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Psychopharmacology (Berl). 2001 Mar;154(3):301-10.

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

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Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.



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.


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


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.


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.


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

[Indexed for MEDLINE]

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