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.