Agonist action at 5-HT1C receptors facilitates 5-HT1A receptor-mediated spontaneous tail-flicks in the rat.
In rats lightly restrained in plastic cylinders, subcutaneous administration of the selective, high efficacy 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), induced spontaneous tail-flicks, that is, tail-flicks in the absence of extraneous stimulation. The putative 5-HT1B receptor agonist, CGS 12066B, the mixed 5-HT1B/1C receptor agonists, 1-((3-(trifluoromethyl)phenyl]piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP), the 5-HT1C/2 receptor agonist, [+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT1B/1C/2 receptor agonist, quipazine, did not, in contrast, elicit tail-flicks when applied alone. However, TFMPP, mCPP, DOI and quipazine, but not CGS 12066B, each potentiated the action of 8-OH-DPAT. Further, in the presence of TFMPP, mCPP and DOI, the dose-response curve for the induction of tail-flicks by 8-OH-DPAT was both steeper and shifted to the left. Tail-flicks induced by another high efficacy 5-HT1A receptor agonist, lisuride, were also enhanced by TFMPP, mCPP and DOI. The 5-HT1A receptor partial agonists, buspirone and (+/-)-flesinoxan, evoked tail-flicks only in the presence of TFMPP, mCPP or DOI. The mixed 5-HT1C/2 receptor antagonists, ritanserin and ICI 169,369, did not modify the action of 8-OH-DPAT alone but abolished the potentiation of 8-OH-DPAT-induced tail-flicks by DOI and TFMPP. Further, the selective 5-HT1A receptor antagonist, BMY 7378, blocked tail-flicks induced by both 8-OH-DPAT alone and 8-OH-DPAT plus DOI or TFMPP. A common property of those drugs potentiating 8-OH-DPAT-induced tail-flicks is an agonist action at 5-HT1C receptors and the data indicate that it is this mechanism which underlies the facilitation of tail-flicks.
Bervoets
K
K
FONDAX, Neurobiology Division, Puteaux, France.
Millan
M J
MJ
Colpaert
F C
FC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D013623:Tail / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D010879:Piperazines; D011810:Quinoxalines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C052561:CGS 12066B; C018406:1-(3-trifluoromethylphenyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin