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.
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References
Abbott A (1987) Can animal model really predict anxiety? TIPS 8:157–158
Bennett DA, Amrick CL (1986) 2-Amino-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam. Life Sci 39:2455–2461
Berridge CW, Dunn AJ (1987) A corticotropin releasing factor antagonist reverses the stress-induced changes of exploratory behavior in mice. Horm Behav 21:393–401
Blanchard DC, Takahashi SN (1988) No change in intermale aggression after amygdala lesions which reduce freezing. Physiol Behav 42:613–616
Bolles RC (1970) Species-specific defensive reactions and avoidance learning. Psychol Rev 71:32–48
Bouton ME, Bolles RC (1980) Conditioned fear assessed by freezing and by the suppression of three different baselines. Anim Learn Behav 8:429–434
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 15:424.2
Costall B, Hendrie CA, Kelly ME, Naylor RJ (1987) Actions of sulpiride and tiapride in a simple model of anxiety in mice. Neuropharmacology 26:195–200
Craft RM, Howard JL, Pollard GT (1988) Conditioned defensive burying as a model for identifying anxiolytics. Pharmacol Biochem Behav 30:775–780
Dunn AJ, File SE (1987) Corticotropin releasing factor has an anxiogenic action in the social interaction test. Horm Behav 21:193–202
Ervin GN, Soroko FS, Cooper BR (1987) Buspirone antagonizes the expression of conditioned taste aversion in rats. Drug Dev Res 11:87–95
Fanselow MS, Helmstetter FJ (1988) Conditioned analgesia, defensive freezing, and benzodiazepines. Behav Neurosci 102:233–243
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 250:100–107
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)
File SE, Baldwin HA (1987) Effects of β-carbolines in animal models of anxiety. Brain Res Bull 19:293–299
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 85:106–110
Hitchcock JM, Davis M (1987) Fear-potentiated startle using an auditory conditioned stimulus: effects of lesions of the amygdala. Physiol Behav 39:403–408
Hjorth S, Engel JA, Carlsson A (1986) Anticonflict effects of low doses of the dopamine agonist apomorphine in the rat. Pharmacol Biochem Behav 24:237–240
Ives JL, Heym J (1989) Antidepressant agents. In: Berger Annual reports in medicinal chemistry. Academic Press, New York
Jackson A, Sanger DJ (1988) Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-d-aspartate receptors? Psychopharmacology 96:87–92
Kalin NH, Sherman JE, Takahashi LK (1988) Antagonism of endogenous CRH systems attenuates stress-induced freezing behavior in rats. Brain Res 457:130–135
Kehne JH, Cassella JV, Davis M (1988) Anxiolytic effects of buspirone and gepirone in the fear-potentiated startle paradigm. Psychopharmacology 94:8–13
Leaton RN, Borszcz GS (1985) Potentiated startle: its relation to freezing and shock intensity in rats. J Exp Psychol: Anim Behav Proc 11:421–428
Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185
McCloskey TC, Paul BK, Commissaris RL (1987) Buspirone effects in an animal conflict procedure: comparison with diazepam and phenobarbital. Pharmacol Biochem Behav 27:171–175
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 24:525–529
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 14:149–167
Sherman JE, Kalin NH (1988) ICV-CRH alters stress-induced freezing without affecting pain sensitivity. Pharmacol Biochem Behav 30:801–807
Shephard RA (1986) Neurotransmitters, anxiety and benzodiazepines: a behavioral review. Neurosci Biobehav Rev 10:449–461
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 43:1103–1110
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 32:259–265
Stephens DN, Meldrum BS, Weidman R, Schneider C, Grutzner M (1986) Does the excitatory amino acid receptor antagonist 2-APH exhibit anxiolytic activity? Psychopharmacology 90:166–169
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 2:285–292
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 18:37–42
Treit D, Fundytus M (1988) A comparison of buspirone and clordiazepoxide in the shock-probe/burying test for anxiolytics. Pharmacol Biochem Behav 30:1071–1075
Treit D, Fundytus M (1989) Thigmotaxis as a test for anxiolytic activity. Pharmacol Biochem Behav 31:959–962
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Conti, L.H., Maciver, C.R., Ferkany, J.W. et al. Footshock-induced freezing behavior in rats as a model for assessing anxiolytics. Psychopharmacology 102, 492–497 (1990). https://doi.org/10.1007/BF02247130
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DOI: https://doi.org/10.1007/BF02247130