Several studies have shown nicotine induces locomotor sensitization in mice and rats by a range of nicotine doses (0.1–2 mg/kg, i.p) and by different schedules of administration (Domino, 2001; Collins and Izenwasser, 2004; Saito et al., 2005). Typically, the first nicotine injection produces locomotor depression which is rapidly overcome by subsequent nicotine exposure and is associated with the development of tolerance to the drug's acute depressant effect (Morrison and Stephenson, 1972). This enhanced locomotor activity in response to repeated nicotine administration is long-lasting (Miller et al., 2001) and central nicotinic receptors play a key role. In support, mecamylamine (Bevins and Besheer, 2001), lobeline (non-selective nAChR antagonists) (Miller et al., 2003), and SSR591813 (α4β2 partial agonist) (Cohen et al., 2003) all blocked induction of sensitization by nicotine. In a separate study, pre-treatment with mecamylamine but not α-bungarotoxin (α7 nAChR antagonist) prevented sensitization, implicating non-α7 nAChRs in mediating the locomotor-stimulant effects of nicotine (Kempsill and Pratt, 2000).
