PMID- 10698011
OWN - NLM
STAT- MEDLINE
DCOM- 20000516
LR  - 20190726
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 39
IP  - 3
DP  - 2000 Jan 28
TI  - GABA(B) receptor antagonists elevate both mRNA and protein levels of the 
      neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor 
      (BDNF) but not neurotrophin-3 (NT-3) in brain and spinal cord of rats.
PG  - 449-62
AB  - In this study we show that single, physiologically-active and non-convulsive 
      doses of the three GABA(B) receptor antagonists CGP 36742, CGP 56433A and CGP 
      56999A increase NGF and BDNF mRNA levels by 200-400% and protein levels by 
      200-250% in rat neocortex, hippocampus as well as spinal cord. In all areas 
      examined the increase in NGF protein preceded that of BDNF. Peak levels of both 
      neurotrophins are transient and occur between 24 and 72 h, depending on the 
      region. In contrast, NT-3 protein concentrations in the neocortex and hippocampus 
      were decreased significantly to 50% of control values within 48-96 h. The 
      decrease in the spinal cord was less than 30% and did not reach significant 
      levels. These data clearly demonstrate that GABA(B) receptor antagonists induce a 
      specific neurotrophin expression in the central nervous system at physiologically 
      relevant doses, as opposed to the extreme conditions of seizure paradigms. The 
      results are in line with the concept that neuronal neurotrophin synthesis and 
      release in brain are controlled by afferent nerve activity. GABA(B) receptor 
      antagonists could therefore be a valuable new approach to selectively increase 
      endogenous neurotrophin levels in the central nervous system.
FAU - Heese, K
AU  - Heese K
AD  - Department of Physiology, University of Basel, Switzerland.
FAU - Otten, U
AU  - Otten U
FAU - Mathivet, P
AU  - Mathivet P
FAU - Raiteri, M
AU  - Raiteri M
FAU - Marescaux, C
AU  - Marescaux C
FAU - Bernasconi, R
AU  - Bernasconi R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (GABA Antagonists)
RN  - 0 (GABA-B Receptor Antagonists)
RN  - 0 (Neurotrophin 3)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA-B)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/*drug effects/metabolism
MH  - GABA Antagonists/*pharmacology
MH  - *GABA-B Receptor Antagonists
MH  - Male
MH  - Nerve Growth Factor/*drug effects/metabolism
MH  - Neurotrophin 3/*drug effects/metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, GABA-B/metabolism
MH  - Spinal Cord/drug effects/metabolism
EDAT- 2000/03/04 09:00
MHDA- 2000/05/20 09:00
CRDT- 2000/03/04 09:00
PHST- 2000/03/04 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 2000/03/04 09:00 [entrez]
AID - S0028390899001665 [pii]
AID - 10.1016/s0028-3908(99)00166-5 [doi]
PST - ppublish
SO  - Neuropharmacology. 2000 Jan 28;39(3):449-62. doi: 10.1016/s0028-3908(99)00166-5.