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Psychopharmacology

, Volume 102, Issue 4, pp 492–497 | Cite as

Footshock-induced freezing behavior in rats as a model for assessing anxiolytics

  • Lisa H. Conti
  • Caroline R. Maciver
  • John W. Ferkany
  • Mary E. Abreu
Original Investigations

Abstract

A number of chemically distinct anxiolytics were examined for effects on defensive behavior (foot-shock-induced freezing) in rats. Central nervous system acting drugs which are not anxiolytics were also studied. Animals were injected with a drug or vehicle (IP) prior to being placed in a chamber with a grid floor through which two footshocks were delivered. Behavior was observed during the pre-shock period (2 min) and for 4 min after the second footshock. The effects of the following drugs on the duration of footshock-induced freezing were studied: diazepam (DZP); 2-amino-4,5-(1,2-cyclohexyl)-7 phosphonoheptonic acid (NPC 12626); 3-((+/−)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP); [(+)-5-methyl-10-11,dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801); buspirone hydrochloride (BUS);dl-amphetamine sulfate (AMP); haloperidol (HAL); ethyl-β-carboline-3 carboxylate (β-CCE). Compounds which reduced the duration of footshock-induced freezing included DZP, BUS, and the competitive NMDA antagonists NPC 12626 and CPP. The non-competitive NMDA antagonist, MK-801, had no effect on the response. The highest dose of amphetamine tested also reduced footshock-induced freezing. However, amphetamine-treated animals did not locomote or rear after footshock, suggesting fear of the environment. Animals injected with DZP, NPC 12626, CPP or buspirone spent at least 1.4 of the 4 post shock minutes locomoting. Haloperidol had no effect on freezing at the doses tested. β-CCE tended to increase the duration of footshock-induced freezing. With the exception of buspirone, none of the compounds which reduced freezing were analgesic in a hot plate test, suggesting that analgesia was not the cause of reduced freezing. Foot-shock-induced freezing is a simple test which may be useful for detecting the anxiolytic potential of drugs from a number of different classes.

Key words

Anxiety model Defensive behavior Anxiolytic NPC 12626 Fear behavior 

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References

  1. Abbott A (1987) Can animal model really predict anxiety? TIPS 8:157–158Google Scholar
  2. Bennett DA, Amrick CL (1986) 2-Amino-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam. Life Sci 39:2455–2461CrossRefPubMedGoogle Scholar
  3. Berridge CW, Dunn AJ (1987) A corticotropin releasing factor antagonist reverses the stress-induced changes of exploratory behavior in mice. Horm Behav 21:393–401CrossRefPubMedGoogle Scholar
  4. Blanchard DC, Takahashi SN (1988) No change in intermale aggression after amygdala lesions which reduce freezing. Physiol Behav 42:613–616CrossRefPubMedGoogle Scholar
  5. Bolles RC (1970) Species-specific defensive reactions and avoidance learning. Psychol Rev 71:32–48Google Scholar
  6. Bouton ME, Bolles RC (1980) Conditioned fear assessed by freezing and by the suppression of three different baselines. Anim Learn Behav 8:429–434Google Scholar
  7. Conti L, Costello D, Loftus R., Martin L, White M, Abreu ME (1989) Effect of chronic CRF administration: behavioral, hormonal and receptor changes. Soc Neurosci Abstr 15:424.2Google Scholar
  8. Costall B, Hendrie CA, Kelly ME, Naylor RJ (1987) Actions of sulpiride and tiapride in a simple model of anxiety in mice. Neuropharmacology 26:195–200CrossRefPubMedGoogle Scholar
  9. Craft RM, Howard JL, Pollard GT (1988) Conditioned defensive burying as a model for identifying anxiolytics. Pharmacol Biochem Behav 30:775–780PubMedGoogle Scholar
  10. Dunn AJ, File SE (1987) Corticotropin releasing factor has an anxiogenic action in the social interaction test. Horm Behav 21:193–202CrossRefPubMedGoogle Scholar
  11. Ervin GN, Soroko FS, Cooper BR (1987) Buspirone antagonizes the expression of conditioned taste aversion in rats. Drug Dev Res 11:87–95CrossRefGoogle Scholar
  12. Fanselow MS, Helmstetter FJ (1988) Conditioned analgesia, defensive freezing, and benzodiazepines. Behav Neurosci 102:233–243PubMedGoogle Scholar
  13. Ferkany JW, Kyle DJ, Willetts J, Rzeszotarski WJ, Guzewska ME, Ellenberger SR, Jones SM, Sacaan AI, Snell LD, Borosky S, Jones BE, Johnson KM, Balster RL, Burchette K, Kawaski K, Hock DB, Dingledine R (1989) Pharmacological profile of NPC 12626, a novel, competitive antagonist for NMDA receptors. J Pharmacol Exp Ther 250:100–107PubMedGoogle Scholar
  14. Ferkany JW, Kyle DJ, Ellenberger WP, Narayanan BA, Hudkins R, Rzeszotarski WJ, Conti L, Enna SJ (1990) Pharmacological profile of novel cyclic analogs of 2-amino-7-phosphonoheptanoic acid. WONIEP VI PROCEEDINGS (in press)Google Scholar
  15. File SE, Baldwin HA (1987) Effects of β-carbolines in animal models of anxiety. Brain Res Bull 19:293–299CrossRefPubMedGoogle Scholar
  16. Hard E, Engel J, Larsson K, Musi B (1985) Effect of diazepam, apomorphine and haloperidol on the audiogenic immobility reaction and on open field behavior. Psychopharmacology 85:106–110CrossRefPubMedGoogle Scholar
  17. Hitchcock JM, Davis M (1987) Fear-potentiated startle using an auditory conditioned stimulus: effects of lesions of the amygdala. Physiol Behav 39:403–408CrossRefPubMedGoogle Scholar
  18. Hjorth S, Engel JA, Carlsson A (1986) Anticonflict effects of low doses of the dopamine agonist apomorphine in the rat. Pharmacol Biochem Behav 24:237–240CrossRefPubMedGoogle Scholar
  19. Ives JL, Heym J (1989) Antidepressant agents. In: Berger Annual reports in medicinal chemistry. Academic Press, New YorkGoogle Scholar
  20. Jackson A, Sanger DJ (1988) Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-d-aspartate receptors? Psychopharmacology 96:87–92PubMedGoogle Scholar
  21. Kalin NH, Sherman JE, Takahashi LK (1988) Antagonism of endogenous CRH systems attenuates stress-induced freezing behavior in rats. Brain Res 457:130–135CrossRefPubMedGoogle Scholar
  22. Kehne JH, Cassella JV, Davis M (1988) Anxiolytic effects of buspirone and gepirone in the fear-potentiated startle paradigm. Psychopharmacology 94:8–13CrossRefPubMedGoogle Scholar
  23. Leaton RN, Borszcz GS (1985) Potentiated startle: its relation to freezing and shock intensity in rats. J Exp Psychol: Anim Behav Proc 11:421–428CrossRefGoogle Scholar
  24. Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185PubMedGoogle Scholar
  25. McCloskey TC, Paul BK, Commissaris RL (1987) Buspirone effects in an animal conflict procedure: comparison with diazepam and phenobarbital. Pharmacol Biochem Behav 27:171–175CrossRefPubMedGoogle Scholar
  26. Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529CrossRefPubMedGoogle Scholar
  27. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167CrossRefPubMedGoogle Scholar
  28. Sherman JE, Kalin NH (1988) ICV-CRH alters stress-induced freezing without affecting pain sensitivity. Pharmacol Biochem Behav 30:801–807CrossRefPubMedGoogle Scholar
  29. Shephard RA (1986) Neurotransmitters, anxiety and benzodiazepines: a behavioral review. Neurosci Biobehav Rev 10:449–461CrossRefPubMedGoogle Scholar
  30. Shibaski T, Yamauchi N, Kato Y, Masuda A, Imaki T, Hotta M, Demura H, Oono H, Ling N, Shizume K (1988) Involvement of corticotropin-releasing factor in restraint stress-induced anorexia and reversion of the anorexia by somatostatin in the rat. Life Sci 43:1103–1110CrossRefPubMedGoogle Scholar
  31. Soderpalm B, Hjorth S, Engel JA (1989) Effects of 5-HT1A receptor agaonists and L-5-HTP in Montgomery's conflict test. Pharmacol Biochem Behav 32:259–265CrossRefPubMedGoogle Scholar
  32. Stephens DN, Meldrum BS, Weidman R, Schneider C, Grutzner M (1986) Does the excitatory amino acid receptor antagonist 2-APH exhibit anxiolytic activity? Psychopharmacology 90:166–169CrossRefPubMedGoogle Scholar
  33. Swederlow NR, Britton KT and Koob GF (1989) Potentiation of acoustic startle by corticotropin-releasing factor (CRF) and by fear are both reversed by α-helical CRF (9–41). Neuropsychopharmacology 2:285–292CrossRefPubMedGoogle Scholar
  34. Tazi A, Dantzer R, LeMoal M, Rivier J, Vale W, Koob GF (1987) Corticotropin-releasing factor antagonist blocks stress-induced fighting in rats. Regul Pept 18:37–42CrossRefPubMedGoogle Scholar
  35. Treit D, Fundytus M (1988) A comparison of buspirone and clordiazepoxide in the shock-probe/burying test for anxiolytics. Pharmacol Biochem Behav 30:1071–1075CrossRefPubMedGoogle Scholar
  36. Treit D, Fundytus M (1989) Thigmotaxis as a test for anxiolytic activity. Pharmacol Biochem Behav 31:959–962CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Lisa H. Conti
    • 1
  • Caroline R. Maciver
    • 1
  • John W. Ferkany
    • 1
  • Mary E. Abreu
    • 1
  1. 1.NOVA Pharmaceutical Corp., CNS PharmacologyBaltimoreUSA

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