Figure 1.

Effects of R-MOD on nicotine self-administration in P-rats. (a) Stable nicotine self-administration maintained by two different doses (30 or 60 μg/kg/infusion, FR-1) of nicotine in rats pretrained on oral sucrose self-administration; (b) active and inactive lever switch results, illustrating that the lever responses were reinforced by nicotine (60 μg/kg/infusion, FR-5), not by previous oral sucrose self-administration; (c) R-MOD (30 and 100 mg/kg) dose-dependently inhibited nicotine self-administration; (d) R-MOD, at the same doses that inhibited nicotine self-administration, had no effect on oral sucrose self-administration. (e) Active lever presses during nicotine self-administration and 3 days of R-MOD replacement for nicotine, illustrating that R-MOD cannot sustain self-administration in P-rats previously self-administering nicotine. (f) Representative records of nicotine or R-MOD self-administration, illustrating a typical pattern of extinction of drug seeking, ie, initial burst-like lever response followed by cessation of lever responding, during 3 h test period after R-MOD substitution for nicotine. *p<0.05; ***p<0.001, compared with predrug baseline in each dose group.