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

Véronique Baudrie, Francis Chaouloff
European Journal of Pharmacology. 1991-06-01; 198(2-3): 129-135
DOI: 10.1016/0014-2999(91)90611-S

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Baudrie V(1), Chaouloff F.

Author information:
(1)Laboratoire de Pharmacologie, CNRS, CHU, Paris, France.

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-HT1A 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.