Skip to main content
SpringerLink
Log in

Serotonin does not mediate anxiolytic effects of buspirone in the fear-potentiated startle paradigm: comparison with 8-OH-DPAT and ipsapirone

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The present study evaluated the role of various neurotransmitter systems in mediating buspirone's blockade of the fear-potentiated startle effect, where acoustic startle amplitude is normally increased in the presence of a light previously paired with a shock. Large lesions of the dorsal and median raphe nuclei or IP injections of the serotonin antagonists cinanserin (10 mg/kg) or cyproheptadine (5 mg/kg) did not alter fear-potentiated startle, nor did these treatments prevent buspirone (5 or 10 mg/kg SC) from blocking fear-potentiated startle. The 5-HT1A agonist 8-OH-DPAT (2.5–10.0) did not block fear-potentiated startle even at doses that produced a marked “5-HT syndrome”. Another 5-HT1A agonist, ipsapirone (10–20 mg/kg), blocked potentiated startle only at a very high dose (40 mg/kg).p-Chlorophenylalanine andp-chloroamphetamine did not alter fear-potentiated startle. Finally, pretreatment with the benzodiazepine receptor antagonist RO-15-1788 (1 mg/kg); the opiate antagonist naloxone (2 mg/kg) or the α2-adrenergic antagonist yohimbine (5 mg/kg) did not reduce fear-potentiated startle, nor did they prevent buspirone from blocking fear-potentiated startle. Taken together, the data do not support the hypothesis that buspirone's anxiolytic effects are mediated by actions at 5-HT1A receptors and more generally indicate that serotonergic neurons do not play an important role in fear-potentiated startle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

    Google Scholar 

  • Andrade R, Nicoll RA (1985) The novel anxiolytic buspirone elicits a small hyperpolarization and seduces serotonin responses at putative 5-HT1 receptors on hippocampal CA1 pyramidal cells. Soc Neurosci Abstr 11:597

    Google Scholar 

  • Archer TA (1982) Serotonin and fear retention in the rat. J Comp Physiol Psychol 96:491–516

    Google Scholar 

  • Berg WK, Davis M (1984) Diazepam blocks fear-enhanced startle elicited electrically from the brainstem. Physiol Behav 32:333–336

    Google Scholar 

  • Cassella JV, Davis M (1986) The design and calibration of a startle measurement system. Physiol Behav 36:377–383

    Google Scholar 

  • Cedarbaum JM, Aghajanian GK (1978) Afferent projections to the rat locus coeruleus as determined by a retrograde tracing technique. J Comp Neurol 178:1–16

    Google Scholar 

  • Commissaris RL, Rech RH (1982) Interactions of metergoline with diazepam, quipazine, and hallucinogenic drugs on a conflict behavior in the rat. Psychopharmacology 76:282–285

    Google Scholar 

  • Davis M (1979a) Diazepam and flurazepam: effects on conditioned fear as measured with the potentiated startle paradigm. Psychopharmacology 62:1–7

    Google Scholar 

  • Davis M (1979b) Morphine and naloxone: effects on conditioned fear as measured with the potentiated startle paradigm. Eur J Pharmacol 54:341–347

    Google Scholar 

  • Davis M, Redmond DE Jr, Baraban JM (1979) Noradrenergic agonists and antagonists: effects on conditioned fear as measured by the potentiated startle paradigm. Psychopharmacology 65:111–118

    Google Scholar 

  • deMontigny C, Blier P, Chaput Y (1984) Electrophysiologically-identified serotonin receptors in the rat CNS. Neuropharmacology 23:1511–1520

    Google Scholar 

  • Eison MS, Eison AS (1984) Buspirone as a midbrain modulator: anxiolysis unrelated to traditional benzodiazepine mechanisms. Drug Dev Res 4:109–119

    Google Scholar 

  • 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

    Google Scholar 

  • Evans L, Moore G (1981) The treatment of phobic anxiety by zimelidine. Acta Psychiatr Scand 63:342–345

    Google Scholar 

  • Glasser T, Traber J (1983) Buspirone: action on serotonin receptors in calf hippocampus. Eur J Pharmacol 88:137–138

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Jacobs BL (1976) Animal behavior model for studying central serotonergic synapses. Life Sci 19:777–786

    Google Scholar 

  • Kehne JH, Cassella JV, Davis M (1987) Anxiolytic effects of buspirone and gepirone in the fear-potentiated startle paradigm. Psychopharmacology 94:8–13

    Google Scholar 

  • Kilts CD, Commissaris RL, Cordon JJ, Rech RH (1982) Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam. Psychopharmacology 78:156–164

    Google Scholar 

  • Koczkas S, Holmberg G, Wedin L (1981) A pilot study of the effect of the 5-HT-uptake inhibitor, zimelidine, on phobic anxiety. Acta Psychiatr Scand 63:328–341

    Google Scholar 

  • Louilot A, LeMoal M, Simon H (1986) A study of the effects of buspirone, BMY 13805, and 1-PP on dopaminergic metabolism in the nucleus accumbens using in vivo voltammetry in freely moving rats. Life Sci 39:685–692

    Google Scholar 

  • Lucki I, Ward HR (1986) Antagonism of serotonin-mediated behaviors in rats by pretreatment with the non-benzodiazepine anxiolytics buspirone or ipsapirone. Soc Neurosci Abstr 12:1236

    Google Scholar 

  • Mauk MD, Peroutka SJ, Kocsis JD (1985) Modulation of synaptic transmission in the hippocampus produced by novel anxiolytics (Buspirone, TVX-Q & DPAT). Soc Neurosci Abstr 11:135

    Google Scholar 

  • McMillen BA, Mattiace LA (1983) Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug. J Neural Transm 57:255–265

    Google Scholar 

  • McMillen BA, McDonald CC (1983) Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat. Neuropharmacology 22:273–278

    Google Scholar 

  • McMillen BA, Matthews RT, Sanghera MK, Shepard PD, German DC (1983) Dopamine receptor antagonism by the novel antianxiety drug, buspirone. J Neurosci 3:733–738

    Google Scholar 

  • Murphy JE (1978) Mianserin in the treatment of depressive illness and anxiety states in general practice. Br J Clin Pharmacol [Suppl 1] 5:81–85

    Google Scholar 

  • Ogren SO (1982a) Central serotonin neurones and learning in the rat. In: Osborne NN (ed) Biology of serotonergic transmission. Wiley, New York, pp 317–334

    Google Scholar 

  • Ogren SO (1982b) Forebrain serotonin and avoidance learning: behavioural and biochemical studies on the acute effect ofp-chloroamphetamine on one-way active avoidance learning in the male rat. Pharmacol Biochem Behav 16:881–895

    Google Scholar 

  • Ogren SO (1985) Central serotonin neurones in avoidance learning: interactions with noradrenaline and dopamine neurones. Pharmacol Biochem Behav 23:107–123

    Google Scholar 

  • Ogren SO, Johansson C (1985) Separation of the associative and non-associative effects of brain serotonin released by p-chloroamphetamine: dissociable serotoninergic involvement in avoidance learning, pain and motor function. Psychopharmacology 86:12–26

    Google Scholar 

  • Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230

    Google Scholar 

  • Peroutka SJ (1985) Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors. Biol Psychiatry 20:971–979

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Riblet LA, Taylor DP, Eison MS, Stanton HC (1982) Pharmacology and neurochemistry of buspirone. J Clin Psychiatry 43:11–16

    Google Scholar 

  • Sanghera MK, German DC (1983) The effects of benzodiazepine and non-benzodiazepine anxiolytics on locus coeruleus unit activity. J Neural Transm 57:267–279

    Google Scholar 

  • Shopsin B, Friedman E, Gershon S (1976) Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients. Arch Gen Psychiatry 33:811–819

    Google Scholar 

  • Skolnick P, Weissman BA, Youdim MBH (1985) Monoaminergic involvement in the pharmacological actions of buspirone. Br J Pharmacol 86:637–644

    Google Scholar 

  • Soubrie P (1986) Reconciling the role of central serotonin neurons in human and animal behavior. Behav Brain Sci 92:319–364

    Google Scholar 

  • Stanton HC, Taylor DP, Riblet LA (1981) Buspirone — an anxioselective drug with dopaminergic action. In: Chronister RB, DeFrance JF (eds) The neurobiology of the nucleus accumbens. Haer Institute, Brunswick, ME, pp 316–321

    Google Scholar 

  • Taylor DP, Riblet LA, Stanton HC, Eison AS, Eison MS, Temple DL Jr (1982) Dopamine and antianxiety activity. Pharmacol Biochem Behav 17:25–35

    Google Scholar 

  • Temple DL Jr, Yevich JP, New JS (1982) Buspirone: chemical profile of a new class of anxioselective agents. J Clin Psychiatry 43:4–9

    Google Scholar 

  • Tricklebank MD, Forler C, Fozard JR (1984) The involvement of subtypes of 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino) tetralin in the rat. Eur J Pharmacol 106:271–282

    Google Scholar 

  • VanderMaelen CP, Matheson GK, Wilderman RC, Patterson LA (1986) Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol 129:123–130

    Google Scholar 

  • Witkin JM, Barrett JE (1986) Interaction of buspirone and dopaminergic agents on punished behavior of pigeons. Pharmacol Biochem Behav 24:751–756

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ribicoff Research Facilities of the Connecticut Mental Health Center and the Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 06508, New Haven, CT, USA

    M. Davis, J. V. Cassella & J. H. Kehne

Authors
  1. M. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. V. Cassella
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. H. Kehne
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davis, M., Cassella, J.V. & Kehne, J.H. 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 (1988). https://doi.org/10.1007/BF00735873

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00735873

Key words

Search

Navigation