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.
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.
Baudrie
V
V
Laboratoire de Pharmacologie, CNRS, CHU, Paris, France.
Chaouloff
F
F
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood; D004837:Epinephrine / Q000097:blood*; D007103:Immobilization; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001786:Blood Glucose; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone; D004837:Epinephrine