Abstract
Fear potentiation of the acoustic startle reflex was produced by eliciting startle responses in the presence of a light that had been previously paired with a shock. Buspirone (0.6–5.0 mg/kg) and gepirone (1.25–10.0 mg/kg), but not their common metabolite, 1-PP (0.5–40 mg/kg), produced a dose-dependent reduction of fear-potentiated startle. These doses of buspirone and gepirone slightly increased baseline startle levels. Reduction of fear-potentiated startle appears to involve supraspinal sites of action, since intraventricular but not intrathecal administration of buspirone (200 μ;g) reduced fear-enhanced startle. Both buspirone and gepirone were highly efficacious in this model compared to other animal tests that are used to study anxiolytic compounds.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aghajanian GK, Sprouse JS, Rasmussen K (1987) Physiology of the midbrain serotonin system. In: Meltzer H, Bunney BS, Coyle JT, Davis K, Kopin IJ, Schuster CR, Shader RI, Simpson GM (eds) Psychopharmacology, the third generation of progress. Raven Press, New York (in press)
Astrachan DI, Davis M (1981) Spinal modulation of the acoustic startle response: the role of norepinephrine, serotonin and dopamine. Brain Res 206:223–228
Berg WK, Davis M (1984) Diazepam blocks fear-enhanced startle elicited electrically from the brainstem. Physiol Behav 32:333–336
Cassella JV, Davis M (1986) The design and calibration of a startle measurement system. Physiol Behav 36:377–383
Chi CI (1965) The effect of amobarbital sodium on conditioned fear as measured by the potentiated startle response in rats. Psychopharmacologia 7:115–122
Davis M (1979a) Diazepam and flurazepam: effects on conditioned fear as measured with the potentiated startle paradigm. Psychopharmacology 62:1–7
Davis M (1979b) Morphine and naloxone: effects on conditioned fear as measured with the potentiated startle paradigm. Eur J Pharmacol 54:341–347
Davis M, Astrachan DI, Gendelman PM, Gendelman DS (1980) 5-Methoxy-N,N-dimethyltryptamine: spinal cord and brainstem mediation of excitatory effects on acoustic startle. Psychopharmacology 70:123–130
Davis M, Gendelman DS, Tischler MD, Gendelman PM (1982) A primary acoustic startle circuit: lesion and stimulation studies. J Neurosci 2:791–805
Davis M, Astrachan DI, Kehne JH, Commissaris RL, Gallager DW (1984) Catecholamine modulation of sensorimotor reactivity measured with acoustic startle. In: Usdin E, Carlsson A, Dahlstrom A, Engel J (eds) Catecholamines: neuropharmacology and central nervous system — theoretical aspects. Liss, New York, pp 245–258
Davis M, Cassella JV, Wrean WH, Kehne JH (1986) Serotonin receptor subtype agonists: differential effects on sensorimotor reactivity measured with acoustic startle. Psychopharmacol Bull 22:837–843
Davis M, Cassella JV, Kehne JH (1987) Serotonin does not mediate anxiolytic effects of buspirone in the fear-potentiated startle paradigm: comparison with 8-OH-DPAT and ipsapirone. Psychopharmacology 94:14–20
Dourish CT, Hutson PH, Curzon G (1986) Putative anxiolytics 8-OH-DPAT, buspirone and TVX Q 7821 are agonists at 5-HT1A autoreceptors in the raphe nuclei. TIPS:212–214
Eison MS (1984) Use of animal models: toward anxioselective drugs. Psychopathology [Suppl 1]: 17:37–44
Eison AS, Eison MS, Stanley M, Riblet LA (1986) Serotonergic mechanisms in the behavioral effects of buspirone and gepirone. Pharmacol Biochem Behav 24:701–707
File SE (1985) Animal models for predicting clinical efficacy of anxiolytic drugs: social behaviour. Neuropsychobiology 13:55–62
Gammons RE, Mayol RF, Eison MS (1983) Concentration of buspirone and 1-pyrimidinylpiperazine, a metabolite, in rat brain. Fed Proc 42:377
Gammons RE, Mayol RF, Labudde JA (1986) Metabolism and disposition of buspirone. Am J Med 80:41–46
Geller I, Hartmann RJ (1982) Effects of buspirone on operant behavior of laboratory rats and cynomologus monkeys. J Clin Psychiatry 43:25–32
Glasser T, Traber J (1983) Buspirone: action on serotonin receptors in calf hippocampus. Eur J Pharmacol 88:137–138
Goldberg ME, Salama AI, Patel JB, Malick JB (1983) Novel benzodiazepine anxiolytics. Neuropharmacology 22:1499–1504
Hitchcock JM, Davis M (1986) Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm. Behav Neurosci 100:11–22
Hjorth, S, Carlsson A (1982) Buspirone: effects on central monoaminergic transmission-possible relevance to animal experimental and clinical findings. Eur J Pharmacol 83:299–303
Kehne JH, Gallager DW, Davis M (1981) Strychnine: brain stem and spinal mediation of excitatory effects on acoustic startle. Eur J Pharmacol 16:111–186
Kehne JH, Astrachan DI, Astrachan E, Tallman JF, Davis M (1986) The role of spinal cord cyclic AMP in the acoustic startle response in rats. J Neurosci 6:3250–3257
Lucki I, Ward HR (1986) Antagonism of serotonin-mediated behaviors in rats by pretreatment with the nonbenzodiazepine anxiolytics buspirone or isapirone. Soc Neurosci Abstr 12:1236
McMillen BA, Mattiace LA (1983) Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug. J Neural Transm 57:255–265
Meert TF, Colpaert FC (1986) The shock probe conflict procedure. A new assay responsive to benzodiazepines, barbiturates and related compounds. Psychopharmacology 88:445–450
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
Peroutka SJ (1985) Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors. Biol Psychiatry 20:971–979
Pich EM, Samanin R (1986) Disinhibitory effects of buspirone and low doses of sulpiride and haloperidol in two experimental anxiety models in rats: possible role of dopamine. Psychopharmacology 89:125–130
Reynolds LS, Seymour PA, Heym J (1986) Inhibition of the behavioral effects of 8-OH-DPAT by the novel anxiolytics buspirone, gepirone and isapirone. Soc Neurosci Abstr 12:481
Riblet LA, Taylor DP, Eison MS, Stanton HC (1982) Pharmacology and neurochemistry of buspirone. J Clin Psychiatry 43:11–16
Tischler MD, Davis M (1983) A visual pathway that mediates fear-conditioned enhancement of acoustic startle. Brain Res 276:55–71
VanderMaelen CP, Matheson GK, Wilderman RC, Patterson LA (1986) Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a nonbenzodiazepine anxiolytic drug. Eur J Pharmacol 129:123–130
Weissman BA, Barrett JE, Brady LS, Witkin JM, Mendelson WB, Paul SM, Skolnick P (1984) Behavioural and neurochemical studies on the anticonflict actions of buspirone. Drug Dev Res 4:83–93
Witkin JM, Barrett JE (1986) Interaction of buspirone and dopaminergic agents on punished behavior of pigeons. Pharmacol Biochem Behav 24:751–756
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kehne, J.H., Cassella, J.V. & Davis, M. Anxiolytic effects of buspirone and gepirone in the fear-potentiated startle paradigm. Psychopharmacology 94, 8–13 (1988). https://doi.org/10.1007/BF00735872
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00735872