CNS dopamine transmission mediated by noradrenergic innervation

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The presynaptic source of dopamine in the CA1 field of dorsal hippocampus is uncertain due to an anatomical mismatch between dopaminergic terminals and receptors. We show, in an in vitro slice preparation from C57BL/6 male mice, that a dopamine (DA) D1 receptor (D1R)-mediated enhancement in glutamate synaptic transmission occurs following release of endogenous DA with amphetamine exposure. It is assumed DA is released from terminals innervating from the ventral tegmental area (VTA) even though DA transporter (DAT)-positive fibers are absent in hippocampus, aregion with abundant D1Rs.Ithas been suggested this results from a lack of DAT expression on VTA terminals rather than a lack of these terminals per se. Neither a knockdown of tyrosine hydroxylase (TH) expression in the VTA by THsiRNA, delivered locally, by adeno-associated viralvector, nor localized pharmacological blockade of DAT to prevent amphetamine uptake into DA terminals, has any effect on the D1R synaptic, enhancement response to amphetamine. However, either a decrease in TH expression in the locus ceruleus (LC) or a blockade of the nor epinephrine (NE) transporter prevents the DA-mediated response, indicating LC terminals can release both NE and DA. These findings suggest noradrenergic fibers may be the primary source of DA release in hippocampus and corresponding DA-mediated increase in synaptic transmission. Accordingly, these data imply the LC may have a role in DA transmission in the CNS in response to drugs of abuse, and potentially, under physiological conditions.

Original languageEnglish (US)
Pages (from-to)6072-6080
Number of pages9
JournalJournal of Neuroscience
Issue number18
StatePublished - May 2 2012

ASJC Scopus subject areas

  • Neuroscience(all)


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