Alcohol and Alcoholism, Vol 34, 35-42, Copyright © 1999 by Medical Council on Alcoholism
W Watson and H Little
Increased ligand binding to dihydropyridine receptors in the central
nervous system after chronic ethanol consumption is thought to contribute
to the withdrawal syndrome. Previous studies demonstrated such changes when
the binding was measured in vitro, which, as the
receptors are voltage-sensitive, may not accurately reflect the binding
in vivo. In the present study, dihydropyridine binding
was measured in vivo in mice, after intravenous
administration of the radioligand. The aim was to determine whether there
was any correlation between such binding and measurements of behavioural
hyperexcitability at different times during the withdrawal phase and after
two different methods of alcohol administration. Measurements were made of
the binding in vivo of
[3H]nitrendipine, at intervals after withdrawal from
chronic ethanol administration, and of the severity of withdrawal as
measured by response to gentle handling. An increase in the in
vivo binding to [3H]nitrendipine was seen
after cessation of chronic ethanol consumption by liquid diet. The binding
was significantly increased at 4 h, when the behavioural changes were
maximal, but not immediately after withdrawal, when the responses to
handling were unchanged. By 24 h after cessation of the ethanol treatment,
no differences in the binding were found, compared with control values; at
this time the withdrawal hyperexcitability had ceased. When alcohol was
given chronically by inhalation, the in vivo
dihydropyridine binding was increased at 3 h from withdrawal of the
ethanol, the time of maximal behavioural hyperexcitability, but no change
was seen 30 min after withdrawal, when no changes in the ratings of
behaviour were found. There was a significant positive correlation in
individual mice between the ratings of handling-induced behaviour at the 3
h interval and the amount of in vivo binding. These
data support the hypothesis that the sites labelled by
[3H]nitrendipine play an important role in
withdrawal hyperexcitability.
ARTICLES
Correlation between increases in dihydropyridine binding in vivo and behavioural signs of ethanol withdrawal in mice
Drug Dependence Unit, Psychology Department, Durham University, South Road, Durham DH1 3LE, UK; Corresponding author
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