The alpha(4)beta(2) agonist SIB 1765F, but not the alpha(7) agonist AR-R 17779, cross-sensitises to the psychostimulant effects of nicotine

Rationale: Repeated administration of nicotine leads to an augmentation of its locomotor activating effects. Although studies have begun to identify t he nicotinic receptor subtype(s) mediating the psychostimulant properties o f nicotine, none as pet have investigated the subtypes which contribute to the process of sensitisation. Objectives: We therefore investigated cross-s ensitisation to nicotine using subjects chronically treated with two nicoti ne subtype-selective agonists in an attempt to identify the relative contri bution of each to the sensitisation process. Methods. Rats received ten dai ly injections of either vehicle, nicotine (0.4 mg/kg), the alpha(7)-agonist AR-R 17779 (20 mg/kg), or the alpha(4)beta(2)-agonist SIE 1765F (3 mg/kg), and their subsequent locomotor response to acute challenge with each of th ese compounds was assessed. Results: Chronic administration of both nicotin e and SIE 1765F3 but not AR-R 17779, resulted in an enhanced locomotor resp onse to acute challenge with either nicotine or SIE 1765F but not AR-R 1777 9. Conclusions: These data support a role for the alpha(4)beta(2) receptor in both the initiation and expression of sensitisation to the psychomotor s timulant effects of nicotine.