The effects of pharmacological blockade of the 5-HT(6) receptor on formalin-evoked nociceptive behaviour, locomotor activity and hypothalamo-pituitary-adrenal axis activity in rats.
5-hydroxytryptamine (5-HT) mediates behavioural and neuroendocrine responses to noxious or stressful stimuli. 5-HT(6) receptors are expressed in brain regions involved in nociceptive processing, however, their role in nociception is unknown. Here we demonstrate that acute, systemic administration of the 5-HT(6) receptor antagonist, 5-chloro-N-(4-methoxy-3-benzothio-phenesulfonamide (SB-271046), reduces formalin-evoked nociceptive behaviour and increases plasma corticosterone. SB-271046 dose-dependently reduced pre-formalin distance moved, rearing, grooming and defecation. These data provide the first evidence for 5-HT(6) receptor-mediated regulation of nociception and hypothalamo-pituitary-adrenal axis activity in a model of persistent pain although effects on locomotor activity demand that the putative antinociceptive effect of SB-271046 be interpreted with some caution.
Finn
David P
DP
Department of Pharmacology and Therapeutics, National University of Ireland, Galway, University Road, Galway, Ireland. David.Finn@Nuigalway.ie
Fone
Kevin C F
KC
Beckett
Simon R G
SR
Baxter
Jonathan A
JA
Ansell
Lucy
L
Marsden
Charles A
CA
Chapman
Victoria
V
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003672:Defecation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity; D006120:Grooming / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013312:Stress, Physiological / Q000097:blood / Q000139:chemically induced; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; D005557:Formaldehyde; C117443:SB 271046; D003345:Corticosterone