Imidazenil, a
benzodiazepine recognition site
ligand that acts as partial positive allosteric modulator of
gamma-aminobutyric acid (
GABA) action at GABAA receptors, inhibits in a dose-dependent manner (0.56-2.5 micromol/kg i.p. to rats) the
cocaine-induced increase in
dopamine (DA) content in the
dialysates of the nucleus accumbens shell and striatum and also inhibits
cocaine-induced locomotor activity.
Diazepam, a full allosteric modulator of
GABA action at GABAA receptors, in a dose of 4.4 micromol/kg i.p. also attenuates the
cocaine-induced increase in DA content in the
dialysates of nucleus accumbens shell, and striatum and the
cocaine-induced locomotor activity. However,
imidazenil (2.5 micromol/kg i.p.) fails to reduce spontaneous locomotor activity, whereas
diazepam (4.4 micromol/kg i.p.) elicits sedation and
ataxia and clearly impairs spontaneous locomotor activity. When added in vitro, both
imidazenil and
diazepam potentiate the
GABA-mediated reduction of the ventral tegmental area DA neuron firing rate. After protracted treatment (14 days/three times a day with an increasing-dose schedule), the inhibitory actions of
imidazenil fail to develop tolerance, whereas the actions of
diazepam exhibit high tolerance liability. We conclude that
imidazenil is devoid of tolerance liability and that, via a GABAA-mediated reduction in the extracellular DA in nucleus accumbens shell, it might reduce the psychomotor activity and reinforcing properties of
cocaine.