Effects of FG 7142, a putative anxiogenic, on response and preference in an anxiolytic-sensitive conflict schedule

Eleven rats' lever responses during one discriminative stimulus produced food on a variable-interval schedule, and responding during another stimulus produced both food (on a richer schedule) and intermittent shock punishment. Six of the rats could also switch between the punished and unpunished components, providing a measure of preference. Four doses of a benzodiazepine-receptor inverse agonist, FG 7142 (1, 3, 10, and 30 mg/kg, i.p.) were compared to vehicle. The drug dose-dependently reduced unpunished responding. Punished responding was unaffected. Although preference was not significantly affected, the drug suppressed choice responding nonselectively. In contrast, Thomas, Weiss, & Schindler (1990) found that chlordiazepoxide, an anxiolytic benzodiazepine agonist, increased punished responding and preference for the punished component in the same subjects. These differences between the effects of agonists and inverse agonists have implications concerning the classification of inverse agonists as anxiogenic and for the choice of behavioral tests for anxiogenic properties of drugs.