An AMPA receptor potentiator modulates
hippocampal expression of BDNF: an in vivo study

by
Mackowiak M, O'Neill MJ,
Hicks CA, Bleakman D, Skolnick P.
Eli Lilly and Co Ltd,
Lilly Corporate Center,
Indianapolis, IN 46285-0814, USA.
mackow@if-pan.krakow.pl
Neuropharmacology 2002 Jul;43(1):1-10


ABSTRACT

AMPA receptor activation has been demonstrated to increase the neuronal expression of brain derived neurotrophic factor (BDNF). In the present study, we investigated the effect of a novel AMPA receptor potentiator (LY404187) and its active isomer (LY451646) on the expression of BDNF protein and mRNA, as well as TrkB mRNA in rat hippocampus. LY404187 administered for 7 days (1 mg/kg) significantly increased the number of BDNF immunopositive cells in the dentate gyrus, but not other hippocampal subfields. Chronic treatment (7 days) with LY451646 (0.5 mg/kg, comparable to 1 mg/kg of LY404187) increased the level of both BDNF and TrkB mRNA expression in the dentate gyrus, CA3 and CA4 of the hippocampus. However, chronic treatment with lower doses of LY451646 (0.125 and 0.25 mg/kg) decreased the level of BDNF and TrkB mRNA in hippocampus, whilst the highest used dose of LY451646 (1 mg/kg) had no effect on BDNF and TrkB mRNA in hippocampus. In contrast, acute treatment with LY451646 produced an increase in BDNF mRNA levels at doses of 0.125 and 0.25 mg/kg in the hippocampus (CA4, CA3 and dentate gyrus, but not in CA1). LY451646 at 0.5 mg/kg had no effect, but at 1.0 mg/kg decreased the level of BDNF mRNA in hippocampus. Acute treatment with LY451646 did not affect the TrkB receptor mRNA levels in hippocampus. Our results demonstrate that biarylpropylsulfonamide AMPA receptor potentiators are capable of modulating the expression of BDNF and TrkB mRNA in a dose- and time-dependent manner. The increase in both BDNF protein and mRNA expression in the dentate gyrus but not in CA1 indicates a specific role of AMPA receptors in the regulation of BDNF expression in this hippocampal subfield. The regulation of BDNF expression by biarylpropylsulfonamids such as LY451646 may have important therapeutical implications for this class of molecule in the treatment of depression and other CNS disorders.
BDNF
CREB
Options
Exercise
Sexercise
21st Century
CREB and BDNF
Antidepressants
Atypical depression
Retarded depression
BDNF and social defeat
BDNF and new brain cells
Nootropics ('smart drugs')
How do antidepressants work?
Antidepressants and new brain cells
Social isolation selectively reduces BDNF
AMPA receptor potentiators as antidepressants
AMPA receptor potentiation to combat depression
Brain-derived neurotrophic factor (BDNF) and mental health
Effects of electroconvulsive seizures and antidepressants on BDNF
The highs and lows of AMPA-type glutamate receptor subunits in the NaC


Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family