CARDIOVASCULAR AND SOMATIC STARTLE AND DEFENSE - CONCORDANT AND DISCORDANT ACTIONS OF BENZODIAZEPINE RECEPTOR AGONISTS AND INVERSE AGONISTS

Benzodiazepine receptor (BZR) agonists and inverse agonists yield gene rally opposing effects on GABAergic transmission, and the functional c onsequences of these ligands are often bidirectional. BZR agonists exe rt anxiolytic effects, whereas the BZR partial inverse agonist FG 7142 has been reported to have anxiogenic actions in a variety of paradigm s. In keeping with this literature, we found that the cardioaccelerato ry defensive response is enhanced by FG 7142, and attenuated by the BZ R agonist chlordiazepoxide. In contrast, both compounds attenuated bas al 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 o r features of fear and anxiety. The results are consistent with the su ggestion that FG 7142 may selectively enhance those aspects of anxiety that depend on cortical-cognitive processing. (C) 1998 Elsevier Scien ce B.V.