title: Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal.
abstract: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Akbarian
authors.forename: B
authors.initials: B
authors.lastname: Bates
authors.forename: R J
authors.initials: RJ
authors.lastname: Liu
authors.forename: S L
authors.initials: SL
authors.lastname: Skirboll
authors.forename: T
authors.initials: T
authors.lastname: Pejchal
authors.forename: V
authors.initials: V
authors.lastname: Coppola
authors.forename: L D
authors.initials: LD
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Fan
authors.forename: J
authors.initials: J
authors.lastname: Kucera
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.forename: L
authors.initials: L
authors.lastname: Tessarollo
authors.forename: B E
authors.initials: BE
authors.lastname: Kosofsky
authors.forename: J R
authors.initials: JR
authors.lastname: Taylor
authors.forename: M
authors.initials: M
authors.lastname: Bothwell
authors.forename: E J
authors.initials: EJ
authors.lastname: Nestler
authors.forename: G K
authors.initials: GK
authors.lastname: Aghajanian
authors.forename: R
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: 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
chemical_list: 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