Cardiovascular and somatic startle and defense: Concordant and discordant actions of benzodiazepine receptor agonists and inverse agonists

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Benzodiazepine receptor (BZR) agonists and inverse agonists yield generally opposing effects on GABAergic transmission, and the functional consequences of these ligands are often bidirectional. BZR agonists exert anxiolytic effects, whereas the BZR partial inverse agonist FG 7142 has been reported to have anxiogenic actions in a variety of paradigms. In keeping with this literature, we found that the cardioacceleratory defensive response is enhanced by FG 7142, and attenuated by the BZR agonist chlordiazepoxide. In contrast, both compounds attenuated basal and fear-potentiated somatic startle responses. This did not appear to reflect a global reduction of startle reactivity, however, as the cardiac startle response was not significantly altered. These findings support the view that multiple substrates underlie distinct aspects or features of fear and anxiety. The results are consistent with the suggestion that FG 7142 may selectively enhance those aspects of anxiety that depend on cortical-cognitive processing.