Acute and lasting effects of FG-7142 on defensive and approach-attack behavior in cats—implications for models of anxiety which use response suppression
Restricted accessResearch articleFirst published online January, 1991
Acute and lasting effects of FG-7142 on defensive and approach-attack behavior in cats—implications for models of anxiety which use response suppression
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.
Get full access to this article
View all access options for this article.
References
1.
Ableitner A., Herz A. ( 1987) Changes in local cerebral glucose utilization induced by the β-carboline FG-7142 and DMCM reveal structures involved in the control of anxiety and seizure activity. J Neurosci7: 1049
2.
Adamec R. (1974) Neural correlates of long-term changes in predatory behavior in the cat. PhD Dissertation, McGill University
3.
Adamec R.E. (1976a) Hypothalamic and extrahypothalamic substrates of predatory attack suppression and the influence of hunger. Brain Res106: 57-69
4.
Adamec R. (1976b) The interaction of hunger and preying in the domestic cat (Felis catus): an adaptive hierarchy? Behav Biol18: 263-272
5.
Adamec R.E. (1978) Normal and abnormal limbic system mechanisms of emotive biasing. In Livingston K E, Hornykiewicz O (eds), Limbic mechanisms. Plenum Press, New York, pp. 405-455
6.
Adamec R. (1990) Kindling, anxiety and limbic epilepsy: human and animal perspectives. In Wada J A (ed.), Kindling Raven Press, 4. New York , pp. 329-341
7.
Adamec R. (1991a) Partial kindling of the ventral hippocampus : identification of changes in limbic physiology which accompany changes in feline defense and aggression. Physiol Behav, 49 (in press)
8.
Adamec R. (1991b) Individual differences in temporal lobe sensory processing of threatening stimuli in the cat. Physiol Behav , 49 (in press)
9.
Adamec R. (1991c) The effects of corticotrophin releasing factor (CRF) and handling stress on behavior in the elevated plus maze test of anxiety . Submitted for publication
10.
Adamec R., Stark-Adamec C. (1983a) Partial kindling and emotional bias in the cat: lasting after-effects of partial kindling of the ventral hippocampus, I: behavioral changes, Behav Neur Biol38: 205-222
11.
Adamec R., Stark-Adamec C. (1983b) Partial kindling and emotional bias in the cat: lasting after-effects of partial kindling of the ventral hippocampus, II: physiological changes, Behav Neur Biol38: 223-239
12.
Adamec R.E., Stark-Adamec C. (1983c) Limbic control of aggression in the cat. Prog Neuro-Psychopharmacol Biol Psychiat7: 505-512
13.
Adamec R., Stark-Adamec C., Livingston K.E. (1980a) The development of predatory aggression and defense in the domestic cat (Felis catus). I. Effects of early experience on adult patterns of aggression and defense. Biology30: 389-409
14.
Adamec R., Stark-Adamec C., Livingston K.E. (1980b) The development of predatory aggression and defense in the domestic cat (Felis catus). II. Development of aggression and defense in the first 164 days of life. Behav Neur Biol30: 410-434
15.
Adamec R., Stark-Adamec C., Livingston K.E. (1980c) The development of predatory aggression and defense in the domestic cat (Felis catus). III. Effects on development of hunger between 180 and 365 days of age. Behav Neur Biol30: 435
16.
Adamec R.E., Stark-Adamec C., Livingston K.E. (1983) The expression of an early developmentally emergent defensive bias in the adult domestic cat (Felis catus) in non-predatory situations . Appl Animal Ethol10: 89
17.
Andrew R.J. (1972) The information potentially available in mammalian displays. In Hinde R A (ed.), Non-verbal communication. Cambridge University Press, London, pp. 179-206
18.
Britton K.T., Lee G., Koob G.F. (1988) Corticotrophin releasing factor and amphetamine exaggerate partial agonist properties of benzodiazepine antagonist Ro 15-1788 in the conflict test. Psychopharmacology94: 306-311
19.
Charney D.S., Redmond D.E. (1983) Neurobiological mechanisms in human anxiety. Neuropharmacology22: 1531-1536
20.
Chiu T.H., Rosenberg H.C. (1982) Conformational changes in benzodiazepine receptors induced by the antagonist RO-15-1788, Mol Pharmacol23: 289-294
21.
Chopin P., Briley M. (1987) Animal models of anxiety: the effects of compounds that modify 5-HT neurotransmission. Trends Pharmacol Sci8: 383-388
22.
Clineschmidt B.V., Williams M., Witoslawski J.J., Buting P.R., Risley E.A., Totaro J.A. (1982) Restoration of shock-suppressed behavior by treatment with (+)-5-methyl-10,11- dihydro - 5H - dibenzo[a,d]cyclohepten-5,10-imine (MK801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev Res2: 149-163
23.
Cole B.J., Koob G.F. (1988) Propranolol antagonizes the enhanced conditioned fear produced by corticotrophin releasing factor. J Pharmacol Exp Ther247: 902-910
24.
Corda M.G., Giorgi O., Longoni B., Biggio G. (1988) Decreased sensitivity to diazepam induced by chronic administration of FG 7142. Neurosci Lett86: 219-224
25.
Crawley J.N., Ninan P.T., Pickar D., Chrousos M., Linnoila M., Skolnick P., Paul S.M. (1985) Pharmacological antagonism of carboline induced anxiety in rhesus monkeys. J Neurosci5: 485-497
26.
Dorow R., Horowski R., Paschelke G., Amin M., Braestrup C. (1983) Severe anxiety induced by FG-7142, a β-carboline ligand for benzodiazepine receptors. Lancetii: 98-99
File S.E., Pellow S. (1984) The anxiogenic action of FG-7142 in the social interaction test is reversed by chlordiazepoxide and RO-15-1788 but not by CGS 8216. Arch Int Pharmacodyn271: 198-205
29.
File S.E., Lister R.G., Nutt D.J. (1982) The anxiogenic action of benzodiazepine antagonists . Neuropharmacology21: 1033-1037
30.
File S.E., Dingemanse J., Friedman H.L., Greenblatt D.J. (1986) Chronic treatment with RO-15-1788 distinguishes between its benzodiazepine antagonist, agonist and inverse agonist properties . Psychopharmacology89: 113-117
31.
Grant E.C., Mackintosh J.H. (1963) A comparison of social postures of some common laboratory rodents. Behaviour21: 246-259
32.
Hoffmeister F., Wuttle W. (1969) On the actions of psychotropic drugs on the attack and aggressive-defensive behaviour of mice and cats. In Grattini S, Sig E B (eds), Aggressive behaviour. Excerpta Medica Foundation , Amsterdam, pp. 273-280
33.
Jeevanjee F., Little H.J., Martin I.L., Nicholass J.M., Nutt D.J. (1985a) Is FG-7142 mediated kindling due to changes in efficacy at the benzodiazepine/GABA receptor complex? Br J Pharmacol Proc Suppl84: 186P
34.
Jeevanjee F., Little H.J., Nicholass J.M., Nutt D.J. (1985b) Is chronic administration of the benzodiazepine receptor ligand FG-7142 anxiogenic? Br J Pharmacol Proc Suppl84: 188P
35.
Langfeldt T., Ursin H. (1971) Differential action of diazepam on flight and defense behavior in the cat. Psychopharmacol19: 61-66
36.
Leyhausen P. (1965) Uber die funktion der relativen stimmungeshiearchie , Zeitschr Tierpsychol22: 412
37.
Lister R.G., Greenblatt D.J., Abernathy D.R., File S.E. (1984) Pharmacokinetic studies on RO-15-1788, a benzodiazepine receptor ligand in the brain of the rat, Brain Res290: 183-186
38.
Maeda H. (1976) Effects of psychotropic drugs upon the hypothalamic rage responses in cats. Folia Psychiat Neurol Jap30: 539-546
39.
Maeda H., Hirata K. (1978) Two-stage amygdaloid lesions and hypothalamic range: a method useful for detecting functional localization. Physiol Behav8: 529-530
40.
Morgan P.F., Lloyd H G E, Stone T.W. (1983) Inhibition of adenosine accumulation by a CNS benzodiazepine antagonist (RO-15-1788) and a peripheral benzodiazepine receptor ligand (Ro 05-4864). Neurosci Lett41: 183-185
41.
Nutt D.J., Costello M.J. (1988) Rapid induction of lorazepam dependence and reversal with Flumazenil. Life Sci43: 1045-1053
42.
Ongini E. (1983) Behavioral and EEG effects of benzodiazepines and their antagonists in the cat. In Biggio G , Costa E (eds), Benzodiazepine recognition site ligands: biochemistry and pharmacology. Raven Press, New York, pp. 211-225
43.
Polc P., Bonetti E.P., Schaffner R., Haefely W. (1982) A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers, β-carbolines, and phenobarbitone. Naunyn-Schmiedeberg's Arch Pharmacol321 : 260-264
44.
Skolnick P., Ninan P., Insel T., Crawley J., Paul S. ( 1984) A novel chemically induced animal model of human anxiety . Psychopathology17: 25-36
45.
Stanford S.C., Little H.J., Nutt D.J., Taylor S.C. (1986) A single dose of FG 7142 causes long-term increases in mouse cortical β-adrenoceptors. Eur J Pharmacol134: 313-319
46.
Stephenson F. (1987) Benzodiazepines in the brain. Trends Neurosci10: 185-186
47.
Stoddard S.L., Bergdall V.K., Townsend D.W., Levin B.E. (1986a) Plasma catecholamines associated with hypothalamically-elicited defense behavior. Physiol Behav36: 867-873
48.
Stoddard S.L., Bergdall V.K., Townsend D.W., Levin B.E. (1986b) Plasma catecholamines associated with hypothalamically-elicited flight behavior. Physiol Behav37: 709-715
49.
Stoddard S.L., Bergdall V.K., Conn P.S., Levin B.E. (1987) Increases in plasma catecholamines during naturally elicited defensive behavior in the cat. J Auton Nerv Sys19: 189-195
50.
Thatcher-Britton K., Koob G.F. (1988) Behavioral effects of corticotrophin releasing factor. In Schatzberg A E, Nemeroff C B (eds), The hypothalamic-pituitary-adrenal axis: physiology, pathophysiology and psychiatric implications. Raven Press, New York, pp. 55-66
51.
Thiebot M-H., Soubrie P., Sanger D. (1988) Anxiogenic properties of beta-CCE and FG 7142: a review of promises and pitfalls. Psychopharmacology94: 452-463
52.
Winer B.T. (1962) Statistical principles in experimental design. McGraw-Hill, New York, p. 375
53.
Wolgin D.L., Servidio S. (1979) Disinhibition of predatory attack in kittens by oxazepam. Soc Neurosci Abstr No. 2282; 5: 667
