Psychotogenic properties of benzodiazepine receptor inverse agonists.
Psychopharmacology June 1, 2001 M Sarter, J P Bruno, G G Berntson
The benzodiazepine receptor partial inverse agonist FG 7142, traditionally labeled anxiogenic, is proposed to model core components of schizophrenia theories. FG activates the mesolimbic dopaminergic system, disinhibiting corticopetal cholinergic projections via increased dopamine in the nucleus accumbens. This is hypothesized to mediate hyperattentional impairments contributing to psychotic cognition. FG-induced abnormal processing of conditioned stimuli explains its anxiogenic effects. In rats and monkeys, typical and atypical antipsychotic drugs attenuated FG-induced increases in cortical cholinergic activity and cognitive impairments. Compared to amphetamine and phencyclidine, FG offers an alternative psychotogenic manipulation for research on cortical and cognitive aspects of schizophrenia theories.