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 present study, however, reveals that both the benzodiazepine receptor agonist, chlordiazepoxide and the partial inverse agonist, FG7142, yield a dose-dependent (2-16 mg/kg, i.p) reduction in the amplitude of the acoustic startle response in the rat. The similarity in drug effects on startle was not attributable to congruent effects on basal somatic activity, as chlordiazepoxide resulted in a dose-dependent decrease in activity whereas FG7142 was associated with a small but non-significant increase in activity. As these results contrast with the bidirectional actions of benzodiazepine receptor agonists and inverse agonists in behavioural tests of fear or anxiety, the neuronal mechanisms mediating the effects of benzodiazepine receptor ligands on the acoustic startle response may be distinct from those that underlie the specific fear- attenuating and potentiating actions, respectively, of benzodiazepine receptor agonists and inverse agonists.
Department of Psychology and Neuroscience Program, The Ohio State University, 48 Townshend Hall, Columbus, OH 43210, USA.
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Berntson
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Sarter
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Ruland
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Hart
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Ronis