Psychotogenic properties of benzodiazepine receptor inverse agonists.
M Sarter, J P Bruno, G G Berntson
Psychopharmacology June 1, 2001 DOI: 10.1007/s002130100756 (opens in new tab) via PubMed
Summary
AI-generated from the abstractThe 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.
Study at a glance
| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Population | Rats and monkeys |
| Interventions | FG 7142 typical and atypical antipsychotic drugs |
| Key finding | Proposes that the drug FG 7142 models core components of schizophrenia's neuronal mechanisms by activating the mesolimbic dopaminergic system and disinhibiting cholinergic projections, with effects attenuated by antipsychotic drugs. |
Abstract
The neurochemical, behavioral, and cognitive effects of the benzodiazepine receptor partial inverse agonist beta-carboline FG 7142 (FG), a drug traditionally described as exhibiting 'anxiogenic' effects, are proposed to model core components of present theories of the neuronal mechanisms of schizophrenia. FG activates the mesolimbic dopaminergic system and, via increases in dopaminergic activity in the nucleus accumbens, disinhibits corticopetal cholinergic projections. The latter effect of FG is hypothesized to mediate the hyperattentional impairments that contribute to the development of psychotic cognition. Furthermore, the FG-induced abnormal overprocessing of conditioned stimuli and contexts provides an explanation of the 'anxiogenic' effects of FG. The FG-induced increases in the activity of cortical cholinergic inputs and the FG-induced cognitive impairments in rats and monkeys were demonstrated to be attenuated by the administration of typical and atypical antipsychotic drugs. Compared to the classic psychotogenic drugs amphetamine and phencyclidine, the effects of FG serve as an alternative psychotogenic manipulation in research focusing on the cortical and cognitive aspects of current theories of schizophrenia.