Acute and lasting effects of FG-7142 on defensive and approach-attack behavior in cats—implications for models of anxiety which use response suppression

Abstract

The effect of the anxiogenic β-carboline, FG-7142, on defense and approach-attack behavior in the cat was investigated. FG-7142 (10 mg/kg) enhanced defensive responses to rats and mice when tested 10 and 20 min after injection. At the same time, FG-7142 suppressed approach and attack responses to prey. Behavioral effects of FG-7142 were blocked by the specific benzodiazepine receptor blocker RO-15-1788 (10 mg/kg). One or two administrations of FG-7142 were sufficient to produce a lasting (up to 105 days) enhancement of defensive response to rats but not to mice. Defensive response to conspecific threat vocalizations was also lastingly increased. Two injections of FG-7142 produced a lasting suppression of approach-attack on rats only, whereas one injection of FG-7142 did not. The lasting suppression of some measures of approach-attack was found to be independent of the fear-enhancing properties of FG-7142. Tests of the effects of RO-15-1788 on the lasting after-effects of FG-7142 revealed at least two mechanisms which mediate the lasting changes in behavior, one which is dependent upon the benzodiazepine receptor and one which is not. The implications of these findings for rodent models of anxiety which use response suppression to assess fearful 'anxiogenic' effects of drugs are discussed.