PMID- 10234039
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20231014
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 10
DP  - 1999 May 15
TI  - Enhancement of locomotor activity and conditioned reward to cocaine by 
      brain-derived neurotrophic factor.
PG  - 4110-22
AB  - The mesolimbic dopamine (DA) system has been implicated in drug reward, locomotor 
      sensitization, and responding for reward-related stimuli [termed conditioned 
      reinforcers (CR)]. Here, we investigated the effect of brain-derived neurotrophic 
      factor (BDNF), which enhances the survival and function of dopaminergic neurons, 
      on stimulant-induced locomotor sensitization and responding for CR. In experiment 
      1, BDNF was infused into the nucleus accumbens (NAc) or ventral tegmental area 
      over 2 weeks via chronically implanted minipumps (1-2.5 microgram/d), and the 
      psychomotor stimulant effects of cocaine (5-15 mg/kg, i.p.) were studied. We 
      found that BDNF enhanced the initial stimulant effects of cocaine and seemed to 
      facilitate the development of sensitization to repeated cocaine doses. In 
      experiment 2, we studied the effects of intra-NAc BDNF infusions on responding 
      for CR. BDNF-treated rats showed twice as many CR responses compared with 
      controls when saline was first administered. BDNF enhanced responding on the CR 
      lever more than four times that seen in control animals after a cocaine injection 
      (10 mg/kg, i.p.). The enhanced response to cocaine in BDNF-treated animals 
      persisted for more than a month after the BDNF infusions had stopped, indicating 
      long-lasting changes in the mesolimbic DA system caused by BDNF administration. 
      In experiment 3, we examined locomotor sensitization to cocaine in heterozygous 
      BDNF knock-out mice and found that the development of sensitization was delayed 
      compared with wild-type littermates. These results demonstrate the profound 
      effects of BDNF on the enhancement of both cocaine-induced locomotion and 
      facilitation of CR and suggest a possible role for BDNF in long-term adaptations 
      of the brain to cocaine.
FAU - Horger, B A
AU  - Horger BA
AD  - Laboratory of Molecular Psychiatry, Departments of Psychiatry, Pharmacology, and 
      Neurobiology, Yale University School of Medicine, Connecticut Mental Health 
      Center, New Haven, Connecticut 06520, USA.
FAU - Iyasere, C A
AU  - Iyasere CA
FAU - Berhow, M T
AU  - Berhow MT
FAU - Messer, C J
AU  - Messer CJ
FAU - Nestler, E J
AU  - Nestler EJ
FAU - Taylor, J R
AU  - Taylor JR
LA  - eng
GR  - P01 DA008227/DA/NIDA NIH HHS/United States
GR  - DA08227/DA/NIDA NIH HHS/United States
GR  - DA10160/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Nerve Growth Factors)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cocaine/*pharmacology
MH  - Conditioning, Operant/*drug effects
MH  - Dopamine Uptake Inhibitors/*pharmacology
MH  - Drug Synergism
MH  - Female
MH  - Infusion Pumps
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity/*drug effects
MH  - Nerve Growth Factors/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Reward
PMC - PMC6782687
EDAT- 1999/05/11 00:00
MHDA- 1999/05/11 00:01
PMCR- 1999/11/15
CRDT- 1999/05/11 00:00
PHST- 1999/05/11 00:00 [pubmed]
PHST- 1999/05/11 00:01 [medline]
PHST- 1999/05/11 00:00 [entrez]
PHST- 1999/11/15 00:00 [pmc-release]
AID - 3014 [pii]
AID - 10.1523/JNEUROSCI.19-10-04110.1999 [doi]
PST - ppublish
SO  - J Neurosci. 1999 May 15;19(10):4110-22. doi: 10.1523/JNEUROSCI.19-10-04110.1999.