title: Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal.
abstract: Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0 mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-h prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for 1 or 3 weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach-avoidance conflict behavior ("retreats") regarding goal-box entry, reflecting cocaine's dual positive+negative effects. Once established, retreat behaviors persisted over the course of 1 or 3 weeks days of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach-avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli.
authors: Behavioral Pharmacology Laboratory, Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA 93106-9660, USA.
authors: Zu-In
authors: ZI
authors: Su
authors: Gleb
authors: G
authors: Kichaev
authors: Jennifer
authors: J
authors: Wenzel
authors: Osnat
authors: O
authors: Ben-Shahar
authors: Aaron
authors: A
authors: Ettenberg
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001245:Association Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D003463:Cues; D004193:Discrimination Learning; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005059:Euphoria / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D009812:Odorants; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine