Dopamine, but not glutamate, receptor blockade in the basolateral amygdalaattenuates conditioned reward in a rat model of relapse to cocaine-seekingbehavior

Rationale: Following chronic cocaine self-administration and extinction, le sions of the basolateral amygdala (BLA) will significantly attenuate respon ding for secondary reward (tone + light previously paired with cocaine), wi thout disrupting lever responding for primary reward. However, the specific neurotransmitters involved in conditioned reinstatement remain to be deter mined. Objective: In the present study, we examined possible receptor subst rates of amygdalar regulation of conditioned reinstatement after chronic co caine 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 cons equences occurred, selective antagonists of glutamate or dopamine (DA) rece ptors were bilaterally infused at single doses into the BLA prior to testin g for a cocaine-conditioned reward (tone + light). Following three more day s of extinction trials, receptor antagonist effects on reinstatement of coc aine self-administration in the absence of the conditioned stimulus were de termined. Results: Infusion of an NMDA receptor antagonist (AP-5, 1.97 mug/ side), a kainate/alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (CNQX, 0.83 mug/side), or both drugs together ha d no significant effects on conditioned reward or reinstatement of cocaine self-administration. In contrast, infusion of a DA D, receptor antagonist ( SCH-23390, 2 mug/side) or a combination of SCH-23390 and a DA D-2/D-3 recep tor antagonist (raclopride, 5 mug/side) significantly reduced responding fo r conditioned reward, but did not affect cocaine self-administration. Raclo pride alone was without effect on either test day. Conclusions: These resul ts sugdgest that conditioned reinstatement of drug-seeking behavior is depe ndent on amygdalar D-1 receptors.