Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal.
Somatic symptoms and aversion of opiate withdrawal, regulated by noradrenergic signaling, were attenuated in mice with a CNS-wide conditional ablation of neurotrophin-3. This occurred in conjunction with altered cAMP-mediated excitation and reduced upregulation of tyrosine hydroxylase in A6 (locus coeruleus) without loss of neurons. Transgene-derived NT-3 expressed by noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms. Endogenous NT-3 expression, strikingly absent in noradrenergic neurons of postnatal and adult brain, is present in afferent sources of the dorsal medulla and is upregulated after chronic morphine exposure in noradrenergic projection areas of the ventral forebrain. NT-3 expressed by non-catecholaminergic neurons may modulate opiate withdrawal and noradrenergic signalling.
Akbarian
S
S
Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Bates
B
B
Liu
R J
RJ
Skirboll
S L
SL
Pejchal
T
T
Coppola
V
V
Sun
L D
LD
Fan
G
G
Kucera
J
J
Wilson
M A
MA
Tessarollo
L
L
Kosofsky
B E
BE
Taylor
J R
JR
Bothwell
M
M
Nestler
E J
EJ
Aghajanian
G K
GK
Jaenisch
R
R
D000375:Aging; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000235:genetics; D008125:Locus Coeruleus / Q000201:enzymology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020933:Neurotrophin 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D020933:Neurotrophin 3; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005576:Colforsin; D009020:Morphine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase