Buspirone, ipsapirone and 1-(2-pyrimidinyl)-piperazine decrease cold-induced thyrotropin secretion in rats.
The aim of this study was to analyse the effects of the 5-HT1A receptor-related antidepressants/anxiolytics, buspirone and ipsapirone (1-10 mg/kg i.v.), and those of their common metabolite, the alpha 2-adrenoceptor antagonist, 1-(2-pyrimidinyl)-piperazine (1-PP, 1-10 mg/kg i.v.), on cold-induced thyrotropin (TSH) secretion in conscious catheterised rats. The effects of the centrally acting 5-HT1A receptor agonist, 8-hydroxy-2-(d-n-propylamino)tetralin (8-OH-DPAT, 0.1-1 mg/kg i.v.), and of the peripherally acting 5-HT1A receptor agonist, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT, 0.1-1 mg/kg i.v.), were also included in this study. Buspirone, ipsapirone, and 1-PP dose dependently decreased cold-induced TSH secretion throughout the 90 min of analysis. However, the preventive effect of 1-PP was reached with a lower dose (3 mg/kg) than that needed for the parent compound (10 mg/kg). 8-OH-DPAT administration diminished but did not prevent cold-induced TSH secretion, while only the highest dose of DP-5-CT diminished secretion (1 mg/kg). Lastly, the TSH-releasing hormone (TRH)-induced TSH secretion was left unaffected by either buspirone or ipsapirone pretreatment (10 mg/kg), but was diminished by 1-PP pretreatment (3 mg/kg). These data suggest that both central 5-HT1A receptors and alpha 2-adrenoceptors mediate the effects of azapirones on cold-induced TSH secretion.
Laboratoire de Pharmacologie, Groupe de Neuropharmacologie, CNRS, Paris, France.
P
P
Broqua
V
V
Baudrie
M T
MT
Bluet-Pajot
F
F
Chaouloff
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003080:Cold Temperature; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D013972:Thyrotropin; C037921:1-(2-pyrimidinyl)piperazine; D002065:Buspirone