Figure 2.
Group A, left top and bottom panels: Acquisition of stimulus control in a group of four squirrel monkeys trained to discriminate 0.1 mg/kg nicotine from vehicle (saline; Group A). Abscissae: number of training session once single lever training was completed (1–24) and both levers were available (session 25 onward; ie, 33 training sessions: 24 single lever sessions+33 sessions after both levers are available). Ordinates: effect shown as the percentage of lever-press responses occurring on the nicotine-lever (top) and response rates (bottom) following injections of nicotine or vehicle. The horizontal dashed line at 90% nicotine-lever responding (top left panel) indicates the criterion for evidence of discriminative-stimulus control. Each point represents the mean value and the standard error of the mean (SEM). The dose of nicotine (i.m.) was reduced progressively from 0.18 to 0.1 mg/kg in individual subjects when they met criteria (see Methods section). ANOVA confirmed significant main effects of drug treatment (F1,192=49.29; P<0.05), time (F32,192=1.64; P<0.05), and a treatment-by-time interaction (F32,192=4.92; P<0.05) on the percentage of nicotine-appropriate responding. No significant effects on response rates were observed after injections of nicotine or vehicle (treatment: F1,192=0.38; P>0.05; treatment-by-time interaction: F32,192=1.28; P>0.05; bottom panel). A significant effect of time on response rates was obtained (F32,192=3.86; P<0.05), most likely reflecting some increases in the overall rates of responding in all subjects over the course of discrimination training. Group B, right top and bottom panels. Lack of stimulus control in a group of four squirrel monkeys that were treated with SEL-068 and subsequently trained to discriminate 0.18 mg/kg nicotine from vehicle (saline; Group B). See left top and bottom panels of Group A for all other details. ANOVA confirmed no significant effects of drug treatment (Fs1,90⩾0.0002; Ps>0.05), time (Fs15,90⩾0.61; Ps>0.05), or a treatment-by-time interaction (Fs15,90⩾0.7; Ps>0.05) on the percentage of nicotine-appropriate responding and response rates during 0.18 mg/kg nicotine discrimination training.