Muscarinic receptor antagonism in the basolateral amygdala blocks acquisition of cocaine-stimulus association in a model of relapse to cocaine-seeking behavior in rats.
Recent evidence has demonstrated a critical role for the basolateral amygdala complex in the reinstatement of extinguished drug-seeking behavior produced by drug-paired cues. In the current study, we utilized a model of the acquisition and expression of cocaine-stimulus associative pairing in order to study the role of cholinergic input to the basolateral amygdala in mediating conditioned-cued reinstatement. Male, Sprague-Dawley rats were first trained daily to self-administer i.v. cocaine on a fixed ratio 1 schedule of reinforcement. The muscarinic acetylcholine receptor antagonist, scopolamine, was directly infused into the basolateral amygdala prior to: a) classically conditioned pairing of a tone+light stimulus with cocaine infusions (acquisition), or b) testing of conditioned-cued reinstatement following a period of withdrawal from cocaine and extinction of cocaine-paired lever responding. Infusion of scopolamine just prior to the classical conditioning trial produced a dose-dependent disruption of cocaine-seeking behavior maintained by cocaine-paired cues during the reinstatement test. In contrast, infusion of scopolamine prior to the reinstatement test had no effect on conditioned-cued reinstatement of cocaine-seeking behavior. These results indicate a crucial role for cholinergic innervation of muscarinic acetylcholine receptors in the basolateral amygdala during the formation, but not the expression, of stimulus-reward associations that mediate cue-induced cocaine-seeking behavior.
See
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Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue BSB 416A, Charleston, SC 29425, USA. seere@musc.edu
McLaughlin
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Fuchs
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D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000523:psychology; D003042:Cocaine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*; D055502:Secondary Prevention; D012646:Self Administration / Q000523:psychology
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D003042:Cocaine