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5-HT1A receptor-effector system responsivity in panic disorder

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Abstract

To explore 5-HT1A receptor responsivity in panic disorder (PD), hypothermic, neuroendocrine and behavioral responses to the selective partial 5-HT1A receptor agonist ipsapirone (IPS) were investigated in patients with primary PD and healthy controls. Fourteen patients and matched controls received a single oral dose of 0.3 mg/kg IPS or placebo under double-blind, random-assignment conditions. IPS induced hypothermia and corticotropin (ACTH)/cortisol release but had only minimal effects on behavior. Compared with controls, the patients with PD exhibited significantly attenuated thermoregulatory and neuroendocrine responses to IPS. Although the healthy subjects reported increased drowsiness and the PD patients rated themselves more nervous and less calm following administration of IPS, no consistent changes in ratings of anxiety or panic symptoms were recorded. The impaired hypothermic and ACTH/cortisol responses following 5-HT1A receptor activation reflects subsensitivity of both the pre- and post-synaptic 5-HT1A receptor-effector system, thus supporting the hypothesis that a 5-HT1A receptor-related serotonergic dysfunction may be linked to the pathophysiology of PD. Future studies of 5-HT1A receptor-effector complex function in conjunction with assessment of the responsivity of other subtypes (e.g. 5-HT2, 5-HT3) should promote the evaluation of 5-HT system integrity in anxiety disorders and its involvement in anxiolytic drug effects.

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References

  • Anderson IM, Cowen PJ, Grahame-Smith DG (1990) The effect of gepirone on neuroendocrine function and temperature in humans. Psychopharmacology 100:498–503

    Google Scholar 

  • Backus LI, Sharp T Grahame-Smith DG (1990) Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. Br J Pharmacol 100:793–798

    Google Scholar 

  • Charig EM, Anderson IM, Robinson JM, Nutt DJ, Cowen PJ (1986)l-Tryptophan and prolactin release: evidence for 5-HT1 and 5-HT2 receptors. Hum Psychopharmacol 1:93–97

    Google Scholar 

  • Charney DS, Woods SW, Goodman UK, Heninger GR (1987) Serotonin function in anxiety: II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology 92:14–24

    Google Scholar 

  • Chopin P, Briley M (1987) Animal models of anxiety: the effects of compounds that modify 5-HT neurotransmission. TIPS 8:383–387

    Google Scholar 

  • Den Boer JA, Westenberg HGM (1988) Effect of serotonin and noradrenaline uptake inhibitor in panic disorder: a double-blind comparative study with fluvoxamine and maprotiline. Int Clin Psychopharmacol 3:59–74

    Google Scholar 

  • Den Boer JA, Westenberg HGM, Kamerbeeck WDJ (1987) Effect of serotonin uptake inhibitors in anxiety disorders: a double-blind comparison of clomipramine and fluoxetine. Int Clin Psychopharmacol 2:21–32

    Google Scholar 

  • Dillon DJ, Gorman JM, Liebowitz MR (1987) Measurement of lactate-induced panic and anxiety. Psychiatry Res 20:97–105

    Google Scholar 

  • Dourish CT (1987) Brain 5-HT1A receptors and anxiety. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors. Ellis Horwood, Chichester, pp 261–277

    Google Scholar 

  • File SE (1990) Interaction of anxiolytic and antidepressant drugs with hormones of the hypothalamic-pituitary-adrenal axis. Pharmacol Ther 46:357–375

    Google Scholar 

  • Gilbert F, Brazell C, Tricklebank MD, Stahl SM (1988) Activation of the 5-HT1A receptor subtype 147:431–437

    Google Scholar 

  • Gilman AG (1987) G proteins: transduction of receptor-generated signals. Annu Rev Biochem 56:615–649

    Google Scholar 

  • Glennon RA (1990) Serotonin receptors: clinical implications Neurosci Biobehav Rev 14:35–47

    Google Scholar 

  • Goodwin GM, De Souza RJ, Green AR, Heal DJ (1987a) The pharmacology of the behavioural and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Psychopharmacology 91:506–511

    Google Scholar 

  • Goodwin GM, De Souza RJ, Green AR (1987b) Attenuation by electroconvulsive shock and antidepressant drugs of the 5-HT1A receptor-mediated hypothermia and serotonin syndrome produced by 8-OH-DPAT in the rat. Psychopharmacology 91:500–505

    Google Scholar 

  • Gorman JM, Liebowitz MR, Fyer AJ, Goetz D, Campeas RB, Fyer MR, Davies SO, Klein DF (1987) An open trial of fluoxetine in the treatment of panic attacks. J Clin Psychopharmacol 7:329–332

    Google Scholar 

  • Gudelsky GA, Koenig JI, Meltzer HY (1986) Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Neuropharmacology 25:1307–1313

    Google Scholar 

  • Hamik A, Peroutka SJ (1989) 1-(m-Chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain. Biol Psychiatry 25:569–575

    Google Scholar 

  • Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Google Scholar 

  • Hartig PR (1989) Molecular biology of 5-HT receptors. TIPS 10:64–69

    Google Scholar 

  • Hollander E, Fay M, Cohen B, Campeas R, Gorman JM, Liebowitz MR (1988) Serotonergic and noradrenergic sensitivity in obsessive-compulsive disorder: behavioral findings. Am J Psychiatry 145:1015–1017

    Google Scholar 

  • Holsboer F (1989) Psychiatric implications of altered limbic-hypothalamic-pituitary-adrenocortical activity. Eur Arch Psychiatr Neurol Sci 238:302–322

    Google Scholar 

  • Kahn RS, Asnis GM, Wetzler S, Van Praag HM (1988a) Neuroendocrine evidence for serotonin receptor hypersensitivity in panic disorder. Psychopharmacology 96:360–364

    Google Scholar 

  • Kahn RS, Wetzler S, Van Praag HM, Asnis GM, Strauman T (1988b) Behavioral indications for serotonin receptor hypersensitivity in panic disorder. Psychiatry Res 25:101–104

    Google Scholar 

  • Kennett GA, Curzon G (1988) Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors. Br J Pharmacol 94:137–147

    Google Scholar 

  • Kennett GA, Marcou M, Dourish CT, Curzon G (1987) Single administration of 5-HT1A agonists decreases 5-HT1A presynaptic, but not postsynaptic receptor-mediated responses: relationship to antidepressant-like action. Eur J Pharmacol 138:53–60

    Google Scholar 

  • Koenig JI, Gudelsky GA, Meltzer HY (1987) Stimulation of corticosterone and β-endorphin secretion in the rat by selective 5-HT receptor subtype activation. Eur J Pharmacol 137:1–8

    Google Scholar 

  • Koenig JI, Meltzer HY, Gudelsky GA (1988) 5-Hydroxytryptamine1A receptor-mediated effects of buspirone, gepirone and ipsapirone. Pharmacol Biochem Behav 29:711–715

    Google Scholar 

  • Kucharik RF, White SM, Moyer JA (1990) Modification of 8-OH-DPAT-induced hypothermia after acute or subchronic ritanserin treatment. Soc Neurosci Abstr 16:850

    Google Scholar 

  • Lesch KP, Rupprecht R, Poten B, Mueller U, Söhnle K, Fritze J, Schulte HM (1989) Endocrine responses to 5-hydroxytryptamine-1A receptor activation by ipsapirone in humans. Biol Psychiatry 26:203–205

    Google Scholar 

  • Lesch KP, Rupprecht R, Poten B, Söhnle K, Schulte HM (1990a) The pharmacology of the hypothermic response to 5-HT1A receptor activation in humans. Eur J Clin Pharmacol 39:17–19

    Google Scholar 

  • Lesch KP, Söhnle K, Poten B, Rupprecht R, Schoellnhammer G, Schulte HM (1990b) Corticotropin and cortisol secretion following central 5-hydroxytryptamine-1A (5-HT1A) receptor activation: effects of 5-HT receptor and β-adrenoceptor antagonists. J Clin Endocrinol Metab 70:670–674

    Google Scholar 

  • Lesch KP, Hoh A, Disselkamp-Tietze J, Wiesmann M, Osterheider M, Schulte HM (1991a) 5-Hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder: comparison of patients and controls. Arch Gen Psychiatry 48:540–547

    Google Scholar 

  • Lesch KP, Aulakh CS, Tolliver TJ, Murphy DL (1991b) Regulation of G proteins by chronic antidepressant drug treatment in rat brain: tricyclics but not dorgyline increase G0α subunits. Eur J Pharmacol 207:360–364

    Google Scholar 

  • Meller E, Goldstein M, Bohmaker K (1990) Receptor reserve for 5-hydroxytryptamine1A-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists. Mol Pharmacol 37:231–237

    Google Scholar 

  • Murphy DL (1990) Neuropsychiatric disorders and the multiple human brain serotonin receptor subtypes and subsystems. Neuropsychopharmacology 3:457–471

    Google Scholar 

  • Murphy DL, Mueller EA, Hill JL, Tolliver TJ, Jacobsen FM (1989) Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers. Psychopharmacology 98:275–282

    Google Scholar 

  • Murphy DL, Lesch KP, Pigott TA (1990) Potential relevance of the partial agonist properties of different serotonergic agents studied in humans to their neuropharmacologic effect. Abstracts of the ACNP 1990 Annual Meeting, p 80

  • Newman ME, Lerer B (1988) Chronic elektroconvulsive shock and desipramine reduce the degree of inhibition by 5-HT and carbachol of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Eur J Pharmacol 148:257–264

    Google Scholar 

  • Nutt DJ, Fraser S (1987) Platelet binding studies in panic disorder. J Affective Disord 12:7–11

    Google Scholar 

  • Rausch JL, Stahl SM, Hauger RL (1990) Cortisol and growth hormone response to the 5-HT1A agonist gepirone in depressed patients. Biol Psychiatry 28:73–78

    Google Scholar 

  • Spielberger CD, Gorsuch RL, Lushene RE (1970) The State-Trait Anxiety Inventory: Test Manual for Form X. Consulting Psychologists Press, Palo Alto

    Google Scholar 

  • Traber J, Glaser T (1987) 5-HT1A receptor-related anxiolytics. TIPS 8:432–437

    Google Scholar 

  • Uhde TW, Berrettini WH, Roy-Byrne PP (1987) Platelet [3H]imipramine binding in patients with panic disorder. Biol Psychiatry 22:52–58

    Google Scholar 

  • Zohar J, Mueller EA, Insel TR, Zohar-Kadouch RC, Murphy DL (1987) Serotonergic responsivity in obsessive-compulsive disorder: comparison of patients and healthy controls. Arch Gen Psychiatry 44:946–951

    Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, University of Würzburg, W-8700, Würzburg, Federal Republic of Germany

    K. P. Lesch, M. Wiesmann, A. Hoh, T. Müller, J. Disselkamp-Tietze & M. Osterheider

  2. Department of Medicine I, University of Kiel, W-2300, Kiel, Federal Republic of Germany

    H. M. Schulte

Authors
  1. K. P. Lesch
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  2. M. Wiesmann
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  3. A. Hoh
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  4. T. Müller
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  5. J. Disselkamp-Tietze
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  6. M. Osterheider
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  7. H. M. Schulte
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Lesch, K.P., Wiesmann, M., Hoh, A. et al. 5-HT1A receptor-effector system responsivity in panic disorder. Psychopharmacology 106, 111–117 (1992). https://doi.org/10.1007/BF02253597

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  • DOI: https://doi.org/10.1007/BF02253597

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