title: The self-administration of rapidly delivered cocaine promotes increased motivation to take the drug: contributions of prior levels of operant responding and cocaine intake.
abstract: BACKGROUND
  Rapid drug delivery to the brain might increase the risk for developing addiction. In rats, increasing the speed of intravenous cocaine delivery (5 vs. 90 s) increases drug intake and the subsequent motivation to self-administer cocaine. Increased motivation for cocaine could result not only from more extensive prior drug intake and operant responding for drug, but also from neuroplasticity evoked by rapid drug uptake.
  
  
  OBJECTIVE
  We determined the contributions of prior drug intake and operant responding to the increased motivation for cocaine evoked by rapid delivery. We also investigated the effects of cocaine delivery speed on corticostriatal expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) mRNA.
  
  
  METHODS
  Rats self-administered cocaine (0.25 mg/kg/infusion) delivered over 5 or 90 s during short-access (1 h/session; ShA) or long-access (6 h; LgA) sessions. Motivation for cocaine was then assessed by measuring responding under a progressive ratio schedule of reinforcement. Next, BDNF and TrkB mRNA levels were measured in 5- and 90-s rats.
  
  
  RESULTS
  Five-second ShA and 5-s-LgA rats were more motivated for cocaine than their 90-s counterparts. This effect was dissociable from previous levels of drug intake or of operant responding for cocaine. In parallel, only rats self-administering rapid cocaine injections had altered BDNF and TrkB mRNA levels in corticostriatal regions.
  
  
  CONCLUSIONS
  Rapid drug delivery augments the motivation for cocaine independently of effects on the levels of drug intake or operant responding for drug. We suggest that rapid delivery might increase the motivation for drug by promoting neuroplasticity within reward pathways. This neuroplasticity could involve increased regulation of BDNF/TrkB.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, H3C 3J7, Canada.
authors.forename: Karim
authors.initials: K
authors.lastname: Bouayad-Gervais
authors.forename: Ellie-Anna
authors.initials: EA
authors.lastname: Minogianis
authors.forename: Daniel
authors.initials: D
authors.lastname: Lévesque
authors.forename: Anne-Noël
authors.initials: AN
authors.lastname: Samaha
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009042:Motivation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D012201:Reward; D012646:Self Administration
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018765:Dopamine Uptake Inhibitors; D020813:Receptor, trkB; D003042:Cocaine
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