Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal

Somatic symptoms and aversion of opiate withdrawal, regulated by noradrener gic 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 c oeruleus) without loss of neurons. Transgene-derived NT-3 expressed by nora drenergic neurons of conditional mutants restored opiate withdrawal symptom s. Endogenous NT-3 expression, strikingly absent in noradrenergic neurons o f postnatal and adult brain, is present in afferent sources of the dorsal m edulla and is upregulated after chronic morphine exposure in noradrenergic projection areas of the ventral forebrain. NT-3 expressed by noncatecholami nergic neurons may modulate opiate withdrawal and noradrenergic signalling.