title: Dopamine D1 or D2 receptor antagonism within the basolateral amygdala differentially alters the acquisition of cocaine-cue associations necessary for cue-induced reinstatement of cocaine-seeking.
abstract: The basolateral amygdala complex has been implicated in the formation and utilization of cocaine-cue associations in rat models of cue-induced reinstatement to cocaine-seeking behavior. We have previously demonstrated the importance of dopamine inputs to the basolateral amygdala complex in the reinstatement of cocaine-seeking behavior following chronic cocaine self-administration. Here we show that selective blockade of amygdalar dopamine D1 and D2 receptors during acquisition of cocaine-cue associations has distinctive effects on subsequent conditioned-cued cocaine-seeking behavior. Male, Sprague-Dawley rats were first trained to self-administer i.v. cocaine on a fixed ratio 1 schedule for 5 days. Subjects then received bilateral, intra-basolateral amygdala complex infusions of a dopamine D1 receptor antagonist (SCH23390, 0.25-2.0 microg/side; experiment 1), a dopamine D2 receptor antagonist (raclopride, 0.625-5.0 microg/side; experiment 2), or vehicle just prior to a single classical conditioning session, during which a light+tone cue was discretely paired with passive infusions of cocaine in the absence of lever responding. Following five additional days of cocaine self-administration and 7-10 days of extinction training, animals underwent multiple tests for cue-induced reinstatement. SCH23390 (2.0 microg/side), administered at the time of cocaine-cue association only, produced an attenuation of reinstatement to cue-induced cocaine-seeking behavior. In contrast, low doses of raclopride potentiated, while a higher dose of raclopride attenuated cue-induced reinstatement. These results demonstrate unique contributions of D1 vs. D2 receptors in mediating dopamine inputs within the basolateral amygdala complex during the formation of cocaine-stimulus associations that are critical for cue-induced reinstatement.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, 29425, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Berglind
authors.forename: J M
authors.initials: JM
authors.lastname: Case
authors.forename: M P
authors.initials: MP
authors.lastname: Parker
authors.forename: R A
authors.initials: RA
authors.lastname: Fuchs
authors.forename: R E
authors.initials: RE
authors.lastname: See
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001244:Association; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003463:Cues; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012054:Reinforcement, Psychology; D055502:Secondary Prevention; D012646:Self Administration
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003042:Cocaine