Repeated treatment with the 5-HT1A receptor agonist, ipsapirone, does not affect 8-OH-DPAT- and stress-induced increases in plasma adrenaline levels in the rat

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Abstract

The aim of this study was to investigate whether 5-HT1A receptor-mediated adrenal catecholamine release undergoes rapid desensitisation. Thus, we measured plasma adrenaline either following the acute administration of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.3 mg/kg i.V.), or during immobilisation stress, in rats pretreated repeatedly with saline or with the 5-HTin1A receptor agonist, ipsapirone (10 mg/kg i.p., t.i.d. for 7 days). Plasma corticosterone and glucose were measured concomitantly. Neither body weight nor basal plasma adrenaline and corticosterone levels were significantly affected by ipsapirone treatment. Conversely, the latter diminished basal plasma glucose levels. While the 8-OH-DPAT-induced elevations in plasma adrenaline remained unaffected by ipsapirone, the 8-OH-DPAT-induced elevations in plasma corticosterone and glucose tended to be diminished by ipsapirone. Ipsapirone treatment modified the kinetics, but not the amount of adrenaline released by stress. On the other hand, stress-induced activation of the corticotropic axis was amplified by ipsapirone. Lastly, ipsapirone treatment again tended to diminish the hyperglycemic response to stress. These results indicate that (i) 5-HT1A receptor-mediated activation of adrenaline release is not desensitised by short-term ipsapirone treatment, (ii) the anxiolytic/ antidepressant effect of ipsapirone may not be explainable in terms of tolerance to some neuroendorinological consequences of stress.

References (47)

  • G.M. Goodwin et al.

    The pharmacology of the hypothermic response in mice to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). A model of presynaptic 5-HT1 function

    Neuropharmacology

    (1985)
  • D.J. Haleem et al.

    8-OH-DPAT increases corticosterone but no other 5-HT1A receptor-dependent responses more in females

    European J. Pharmacol.

    (1989)
  • P.H. Hutson et al.

    Hypothermia induced by the putative 5-HT1A agonists LY 165163 and 8-OH-DPAT is not prevented by 5-HT depletion

    European J. Pharmacol.

    (1987)
  • P.H. Hutson et al.

    Neurochemical and behavioural evidence for mediation of the hyperphagic action of 8-OH-DPAT by 5-HT cell body autoreceptors

    European J. Pharmacol.

    (1986)
  • C.E. Johansson et al.

    The longterm effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on copulatory and exploratory behaviour in male rats

    European J. Pharmacol.

    (1990)
  • G.A. Kennett et al.

    Antidepressantlike action of 5-HT1A agonists and conventional antidepressants in an animal model of depression

    European J. Pharmacol.

    (1987)
  • G.A. Kennett et al.

    Single administration of 5-HT1A agonists decreases 5-HT1a presynaptic but not postsynaptic receptor-mediated responses: relationship to antidepressant-like action

    European J. Pharmacol.

    (1987)
  • J.I. Koenig et al.

    Stimulation of corticosterone and β-endorphin secretion in the rat by selective 5-HT receptor subtype activation

    European J. Pharmacol.

    (1987)
  • L.G. Larsson et al.

    Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT

    Neuropharmacology

    (1990)
  • P. Martin et al.

    Antidepressant-like action of 8-OH-DPAT, a 5-HT1A agonist, in the learned helplessness paradigm: evidence for a postsynaptic mechanism

    Behav. Brain Res.

    (1990)
  • D.N. Middlemiss et al.

    8-Hydroxy-2-(di-n-propylamino)tetralin discriminates between subtypes of the 5-HT1 recognition site

    European J. Pharmacol.

    (1983)
  • J.F. Nash et al.

    Selective cross-tolerance to 5-HT1A and 5-HT2 receptor-mediated temperature and corticosterone responses

    Pharmacol. Biochem. Behav.

    (1989)
  • A. Pazos et al.

    Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors

    Brain Res.

    (1985)
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