1 research outputs found
Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine
Diazepam
is a benzodiazepine receptor agonist with anxiolytic and
addictive properties. Although most drugs of abuse increase the level
of release of dopamine in the nucleus accumbens, here we show that
diazepam not only causes the opposite effect but also prevents amphetamine
from enhancing dopamine release. We used 20 min sampling <i>in
vivo</i> microdialysis and subsecond fast-scan cyclic voltammetry
recordings at carbon-fiber microelectrodes to show that diazepam caused
a dose-dependent decrease in the level of tonic and electrically evoked
dopamine release in the nucleus accumbens of urethane-anesthetized
adult male Swiss mice. In fast-scan cyclic voltammetry assays, dopamine
release was evoked by electrical stimulation of the ventral tegmental
area. We observed that 2 and 3 mg of diazepam/kg reduced the level
of electrically evoked dopamine release, and this effect was reversed
by administration of the benzodiazepine receptor antagonist flumazenil
in doses of 2.5 and 5 mg/kg, respectively. No significant effects
on measures of dopamine re-uptake were observed. Cyclic voltammetry
experiments further showed that amphetamine (5 mg/kg, intraperitoneally)
caused a significant increase in the level of dopamine release and
in the half-life for dopamine re-uptake. Diazepam (2 mg/kg) significantly
weakened the effect of amphetamine on dopamine release without affecting
dopamine re-uptake. These results suggest that the pharmacological
effects of benzodiazepines have a dopaminergic component. In addition,
our findings challenge the classic view that all drugs of abuse cause
dopamine release in the nucleus accumbens and suggest that benzodiazepines
could be useful in the treatment of addiction to other drugs that
increase the level of dopamine release, such as cocaine, amphetamines,
and nicotine