title: Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking.
abstract: Adolescent rats take cocaine more readily than adults, are more sensitive to lower doses of the drug and work harder for it. It remains unknown if adolescent-onset of cocaine use has long-term consequences on adult relapse liability. Therefore, we tested if self-administering cocaine during adolescence impacts subsequent stress-induced reinstatement to cocaine seeking and taking, after a prolonged drug-free period. Adolescent (~P42) or adult (P88) rats self-administered cocaine (0.6 or 1.2 mg/kg/infusion) for 7 or 10 days. Then, they underwent a prolonged drug-free period (21-40 days), after which they were tested for reinstatement of cocaine-seeking (i.e. responding in the absence of cocaine) induced by the stress hormone corticosterone, the pharmacological stressor yohimbine or electric footshock. Studies employed either single extinction session (within-session extinction/reinstatement) or repeated extinction prior to reinstatement (between-session extinction/reinstatement). Finally, in a separate set of experiments, rats underwent a prolonged drug-free period (~40 days) and were then allowed to self-administer cocaine again, using progressive-ratio procedures that appraise the reinforcing efficacy of cocaine. Rats with adolescent-onset of cocaine use showed greater stress-induced reinstatement of cocaine seeking than rats with adult-onset of cocaine use. This was observed across conditions, providing external validity to these results. Groups did not differ on drug taking in progressive-ratio tests. Our studies indicate that experiencing cocaine during adolescence renders subjects particularly responsive to the subsequent effects of stress on drug seeking. This heightened propensity for reinstatement puts adolescent-onset drug users at heightened risk for relapse.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.|Department of Dermatology, Brown University, Providence, RI, USA.
authors.forename: Wai Chong
authors.initials: WC
authors.lastname: Wong
authors.affiliation: Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.|Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Marinelli
mesh_terms: D017668:Age of Onset; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders; D003213:Conditioning, Psychological; D003345:Corticosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D004558:Electric Stimulation; D005108:Extinction, Psychological; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012054:Reinforcement, Psychology; D013315:Stress, Psychological; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D018765:Dopamine Uptake Inhibitors; D015016:Yohimbine; D003042:Cocaine; D003345:Corticosterone
keywords: Age; corticosterone; footshock; relapse; self-administration; yohimbine