PMID- 24752656
OWN - NLM
STAT- MEDLINE
DCOM- 20151012
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 231
IP  - 21
DP  - 2014 Oct
TI  - The self-administration of rapidly delivered cocaine promotes increased 
      motivation to take the drug: contributions of prior levels of operant responding 
      and cocaine intake.
PG  - 4241-52
LID - 10.1007/s00213-014-3576-4 [doi]
AB  - RATIONALE: 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.
FAU - Bouayad-Gervais, Karim
AU  - Bouayad-Gervais K
AD  - Department of Pharmacology, Faculty of Medicine, Universite de Montreal, C.P. 
      6128, Succursale Centre-Ville, Montreal, QC, H3C 3J7, Canada.
FAU - Minogianis, Ellie-Anna
AU  - Minogianis EA
FAU - Levesque, Daniel
AU  - Levesque D
FAU - Samaha, Anne-Noel
AU  - Samaha AN
LA  - eng
GR  - 97841/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140422
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Behavior, Addictive/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cerebral Cortex/drug effects/*metabolism
MH  - Cocaine/*administration & dosage
MH  - Conditioning, Operant/*drug effects
MH  - Corpus Striatum/drug effects/*metabolism
MH  - Dopamine Uptake Inhibitors/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Motivation/*drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/genetics/metabolism
MH  - Reward
MH  - Self Administration
EDAT- 2014/04/23 06:00
MHDA- 2015/10/13 06:00
CRDT- 2014/04/23 06:00
PHST- 2013/10/11 00:00 [received]
PHST- 2014/04/02 00:00 [accepted]
PHST- 2014/04/23 06:00 [entrez]
PHST- 2014/04/23 06:00 [pubmed]
PHST- 2015/10/13 06:00 [medline]
AID - 10.1007/s00213-014-3576-4 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2014 Oct;231(21):4241-52. doi: 
      10.1007/s00213-014-3576-4. Epub 2014 Apr 22.