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Volume 16, Number 10,
Issue of May 15, 1996
pp. 3507-3510
Copyright ©1996 Society for Neuroscience
The Vesicular Monoamine Transporter, in Contrast to the Dopamine
Transporter, Is Not Altered by Chronic Cocaine Self-Administration
in the Rat
Received Jan. 23, 1996; revised Feb. 29, 1996; accepted March 4, 1996.
Julie M. Wilson and
Stephen J. Kish
Human Neurochemical Pathology Laboratory, Clarke Institute of
Psychiatry, Toronto, Ontario, Canada M5T 1R8
Although much evidence suggests that the brain dopamine transporter
(DAT) is susceptible to dopaminergic regulation, only limited
information is available for the vesicular monoamine transporter
(VMAT2). In the present investigation, we used a chronic,
unlimited-access, cocaine self-administration paradigm to determine
whether brain levels of VMAT2, as estimated using
[3H]dihydrotetrabenazine (DTBZ) binding, are
altered by chronic exposure to a dopamine uptake blocker. Previously,
we showed that striatal and nucleus accumbens DAT levels, as estimated
by [3H]WIN 35,428 and
[3H]GBR 12,935 binding, are altered markedly
using this animal model (). However, in sequential
sections from the same animals, [3H]DTBZ
binding was normal throughout the entire rostrocaudal extent of the
basal ganglia (including striatum and nucleus accumbens), cerebral
cortex, and diencephalon, as well as in midbrain and brainstem
monoamine cell body regions, both on the last day of cocaine access and
after 3 weeks of drug withdrawal. These data provide additional
evidence that VMAT2, unlike DAT, is resistant to dopaminergic
regulation.
Key words:
cocaine;
vesicular monoamine transporter;
dihydrotetrabenazine;
quantitative autoradiography;
self-administration;
unlimited access
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