title: The 5-HT₆ serotonin receptor antagonist SB-271046 attenuates the development and expression of nicotine-induced locomotor sensitisation in Wistar rats.
abstract: 5-HT(6) receptors are almost exclusively expressed in the central nervous system, particularly in areas relevant for addictive behaviour. Based on this, together with other data, this receptor may be a viable target for the control of drug abuse. The present study tested the ability of the 5-HT(6) receptor antagonist SB-271046 to attenuate the development and expression of nicotine-induced behavioural sensitisation. Rats were habituated to the test apparatus prior to experimentation (day 0) and locomotor activity recorded. On days 1 and 5, animals were placed in locomotor test apparatus and after 30 min injected with SB-271046 (1, 3, and 6 mg/kg, intraperitoneally IP) or vehicle. Thirty minutes later, nicotine (0.4 mg/kg, subcutaneously SC) or saline were administered and activity recorded for 60 min. On days 2, 3 and 4 treatments were performed in the home cage. After 17 days of withdrawal (day 23), a challenge test was performed with nicotine (0.4 mg/kg SC) or saline. In a separate experiment of similar design the effects of SB-271046 (1, 3, and 6 mg/kg IP) was tested for its ability to reduce the expression of behavioural sensitisation (day 23). SB-271046 dose dependently reduced the development and expression of nicotine sensitisation vs respective controls. In conclusion, the 5-HT(6) receptor antagonist SB-271046 reduced both the development and expression of nicotine sensitisation, suggesting that the 5-HT(6) receptor may be a viable target for the control of nicotine abuse. Further studies are warranted to substantiate this conclusion and further understand the role of 5-HT(6) receptors in addiction.
authors.affiliation: Abbott Healthcare Products BV, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
authors.forename: N M W J
authors.initials: NM
authors.lastname: de Bruin
authors.forename: B M
authors.initials: BM
authors.lastname: Kloeze
authors.forename: A C
authors.initials: AC
authors.lastname: McCreary
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000737:chemistry*; D055502:Secondary Prevention; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; D009538:Nicotine; C117443:SB 271046