title: Prior extended daily access to cocaine elevates the reward threshold in a conditioned place preference test.
abstract: We have previously shown that extended-access subjects exhibit heightened motivation for cocaine in the runway model, as reflected by reduced number of retreats. This heightened motivation could reflect either an increase in cocaine-induced reward or a decrease in cocaine-induced aversion. The current experiment was therefore devised to assess the cocaine-induced reward and aversion in extended-access rats using a place conditioning test. Rats trained to lever press for intravenous (IV) cocaine (0.25 mg/infusion) were provided 6-hour daily access to the drug over 10 days. Lever pressing in control subjects produced IV infusions of saline. Following drug self-administration, subjects underwent place conditioning for the immediate or delayed effects of cocaine (1.0 or 2.5 mg/kg, IV). In control subjects, the immediate effects of the low dose of cocaine produced conditioned places preferences (CPPs), while the delayed effects produced conditioned place aversions (CPAs). In contrast, the animals receiving low cocaine dose for 6 hours, exhibited place aversions but not preferences; an effect that was reversed when the dose of cocaine was increased. Additionally, in the 6-hour group, delayed conditioning was associated with a reduction in zif268 immunoreactivity in the medial prefrontal cortex and nucleus accumbens shell while immediate conditioning was associated with an increase in zif268-positive cells in the central nucleus of the amygdala. Collectively, these data suggest that extended daily access to cocaine produces a shift in the subject's perceived reward threshold that is paralleled by alterations in the activity of both the reward and stress pathways.
authors: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, USA.
authors: Zu-In
authors: ZI
authors: Su
authors: Jennifer
authors: J
authors: Wenzel
authors: Aaron
authors: A
authors: Ettenberg
authors: Osnat
authors: O
authors: Ben-Shahar
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009042:Motivation; D009714:Nucleus Accumbens / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D003042:Cocaine
keywords: Allostatic theory; cocaine; conditioned place aversions; conditioned place preferences; drug self-administration; immunohistochemistry
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