Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action.

Abstract:

:To assess the role of exocytotic release in signaling by monoamines, we have disrupted the neuronal vesicular monoamine transporter 2 (VMAT2) gene. VMAT2-/- mice move little, feed poorly, and die within a few days after birth. Monoamine cell groups and their projections are indistinguishable from those of wild-type littermates, but the brains of mutant mice show a drastic reduction in monoamines. Using midbrain cultures from the mutant animals, amphetamine but not depolarization induces dopamine release. In vivo, amphetamine increases movement, promotes feeding, and prolongs the survival of VMAT2-/- animals, indicating that precise, temporally regulated exocytotic release of monoamine is not required for certain complex behaviors. In addition, the brains of VMAT2 heterozygotes contain substantially lower monoamine levels than those of wild-type littermates, and depolarization induces less dopamine release from heterozygous than from wild-type cultures, suggesting that VMAT2 expression regulates monoamine storage and release.

journal_name

Neuron

journal_title

Neuron

authors

Fon EA,Pothos EN,Sun BC,Killeen N,Sulzer D,Edwards RH

doi

10.1016/s0896-6273(00)80418-3

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

1271-83

issue

6

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(00)80418-3

journal_volume

19

pub_type

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