Journal
MOLECULAR PSYCHIATRY
Volume 6, Issue 5, Pages 593-604Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4000897
Keywords
locus coeruleus; morphine; addiction; norepinephrine; cre recombinase; pons; medulla
Funding
- NCI NIH HHS [5-R35-CA44339] Funding Source: Medline
- NIDA NIH HHS [1-K08-DA00479] Funding Source: Medline
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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 noncatecholaminergic neurons may modulate opiate withdrawal and noradrenergic signalling.
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