The α₄β₂ agonist SIB 1765F, but not the α₇ agonist AR-R 17779, cross-sensitises to the psychostimulant effects of nicotine

Abstract.

Rationale: Repeated administration of nicotine leads to an augmentation of its locomotor activating effects. Although studies have begun to identify the nicotinic receptor subtype(s) mediating the psychostimulant properties of nicotine, none as yet have investigated the subtypes which contribute to the process of sensitisation. Objectives: We therefore investigated cross-sensitisation to nicotine using subjects chronically treated with two nicotine subtype-selective agonists in an attempt to identify the relative contribution of each to the sensitisation process. Methods: Rats received ten daily injections of either vehicle, nicotine (0.4 mg/kg), the α₇-agonist AR-R 17779 (20 mg/kg), or the α₄β₂-agonist SIB 1765F (3 mg/kg), and their subsequent locomotor response to acute challenge with each of these compounds was assessed. Results: Chronic administration of both nicotine and SIB 1765F, but not AR-R 17779, resulted in an enhanced locomotor response to acute challenge with either nicotine or SIB 1765F but not AR-R 17779. Conclusions: These data support a role for the α₄β₂ receptor in both the initiation and expression of sensitisation to the psychomotor stimulant effects of nicotine.