Apparent hyperalgesic action of the 5-HT1A agonist, 8-OH-DPAT, in the rat reflects induction of spontaneous tail-flicks.
The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), induced a dose-dependent reduction in latency to withdraw the tail from noxious hot water (48 degrees C). However, a similar apparent 'hyperalgesia' was seen at a non-noxious temperature of 38 degrees C. Indeed, 8-OH-DPAT induced spontaneous 'tail-flicks' in the absence of external stimulation. This property was shared by lisuride and LSD, which also have high intrinsic activity at 5-HT1A sites. Agonists at other serotonin (5-HT) receptor types (5-HT1B, 5-HT1C, 5-HT2, 5-HT3) were inactive. Tail-flicks induced by 8-OH-DPAT could be antagonised by the 5-HT1 2 antagonist, methiothepin, but not by ritanserin or GR-38032F, which are antagonists at 5-HT2 and 5-HT3 sites, respectively. Ipsapirone and buspirone, partial 5-HT1A agonists, acted as antagonists. Further, BMY 7378, a proposed selective antagonist at 5-HT1A sites, also blocked the tail-flicks. Thus, the apparent 'hyperalgesia' induced by 8-OH-DPAT may reflect induction of spontaneous tail-flicks. These flicks appear to be mediated by 5-HT1A receptors and represent a novel model of 5-HT1A function in the rat.
Millan
M J
MJ
Fondax Neurobiology Division-Groupe de Recherche Servier, Puteaux, France.
Bervoets
K
K
Colpaert
F C
FC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism; D006941:Hyperesthesia / Q000139:chemically induced*; D008090:Lisuride / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008090:Lisuride