BENZODIAZEPINE RECEPTOR AGONISTS AND INVERSE AGONISTS YIELD CONCORDANT RATHER THAN OPPOSING EFFECTS ON STARTLE RESPONSES

Benzodiazepine receptor agonists and inverse agonists exert generally opposite actions at both the cellular and behavioural levels. The pres ent study, however, reveals that both the benzodiazepine receptor agon ist, chlordiazepoxide and the partial inverse agonist, FG7142, yield a dose-dependent (2-16 mg/kg, i.p.) reduction in the amplitude of the a coustic startle response in the rat. The similarity in drug effects on startle was not attributable to congruent effects on basal somatic ac tivity, as chlordiazepoxide resulted in a dose-dependent decrease in a ctivity whereas FG7142 was associated with a small but non-significant increase in activity. As these results contrast with the bidirectiona l actions of benzodiazepine receptor agonists and inverse agonists in behavioural tests of fear or anxiety, the neuronal mechanisms mediatin g the effects of benzodiazepine receptor ligands on the acoustic start le response may be distinct from those that underlie the specific fear -attenuating and potentiating actions, respectively, of benzodiazepine receptor agonists and inverse agonists.