Muscarinic receptor antagonism in the basolateral amygdala blocks acquisition of cocaine-stimulus association in a model of relapse to cocaine-seeking behavior in rats

• Published in: Neuroscience 2003-01, Vol.117 (2), p.477-483
• Main Authors: See, R.E, McLaughlin, J, Fuchs, R.A
• Format: Article
• Language: English
• Subjects: acetylcholine; Amygdala - drug effects; Animals; Behavior, Addictive - drug therapy; Behavior, Addictive - psychology; Biological and medical sciences; Cocaine - administration & dosage; Cocaine - antagonists & inhibitors; conditioned; cue; Dose-Response Relationship, Drug; Drug addictions; Male; Medical sciences; Muscarinic Antagonists - pharmacology; Muscarinic Antagonists - therapeutic use; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic - physiology; reinstatement; scopolamine; Secondary Prevention; Self Administration - psychology; self-administration; Toxicology
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(02)00665-6

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.