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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
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
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
Archer TA (1982) Serotonin and fear retention in the rat. J Comp Physiol Psychol 96:491–516
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
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
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
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, 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
deMontigny C, Blier P, Chaput Y (1984) Electrophysiologically-identified serotonin receptors in the rat CNS. Neuropharmacology 23:1511–1520
Eison MS, Eison AS (1984) Buspirone as a midbrain modulator: anxiolysis unrelated to traditional benzodiazepine mechanisms. Drug Dev Res 4:109–119
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
Evans L, Moore G (1981) The treatment of phobic anxiety by zimelidine. Acta Psychiatr Scand 63:342–345
Glasser T, Traber J (1983) Buspirone: action on serotonin receptors in calf hippocampus. Eur J Pharmacol 88:137–138
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
Jacobs BL (1976) Animal behavior model for studying central serotonergic synapses. Life Sci 19:777–786
Kehne JH, Cassella JV, Davis M (1987) Anxiolytic effects of buspirone and gepirone in the fear-potentiated startle paradigm. Psychopharmacology 94:8–13
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
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
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
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
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
McMillen BA, Mattiace LA (1983) Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug. J Neural Transm 57:255–265
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
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
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
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
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
Ogren SO (1985) Central serotonin neurones in avoidance learning: interactions with noradrenaline and dopamine neurones. Pharmacol Biochem Behav 23:107–123
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
Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230
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
Sanghera MK, German DC (1983) The effects of benzodiazepine and non-benzodiazepine anxiolytics on locus coeruleus unit activity. J Neural Transm 57:267–279
Shopsin B, Friedman E, Gershon S (1976) Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients. Arch Gen Psychiatry 33:811–819
Skolnick P, Weissman BA, Youdim MBH (1985) Monoaminergic involvement in the pharmacological actions of buspirone. Br J Pharmacol 86:637–644
Soubrie P (1986) Reconciling the role of central serotonin neurons in human and animal behavior. Behav Brain Sci 92:319–364
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
Taylor DP, Riblet LA, Stanton HC, Eison AS, Eison MS, Temple DL Jr (1982) Dopamine and antianxiety activity. Pharmacol Biochem Behav 17:25–35
Temple DL Jr, Yevich JP, New JS (1982) Buspirone: chemical profile of a new class of anxioselective agents. J Clin Psychiatry 43:4–9
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
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
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
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
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00735873