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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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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 µg/side), a kainate/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (CNQX, 0.83 µg/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 µg/side) or a combination of SCH-23390 and a DA D2/D3 receptor antagonist (raclopride, 5 µg/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.

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See, R., Kruzich, P. & Grimm, J. Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior. Psychopharmacology 154, 301–310 (2001).

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