Fig. 3: Intranasal cocaine maintains both low and high rates of responding depending on reinforcement schedule.

A Raster plots showing lever presses over time in a representative animal from the saline (top) and cocaine (bottom) groups during fixed ratio self-administration sessions. Each vertical tick mark represents a lever press. Color indicates fixed ratio schedule: fixed ratio 1 (blue), 2 (turquoise), 5 (red), and 20 (green). B Operant responding across increasing fixed ratio requirements reinforced by intranasal infusion of saline (0.5 µL of 0.9% NaCl per delivery) or cocaine (4 mg/kg cocaine dissolved in 0.5 µL of 0.9% NaCl per delivery). As expected, high doses of cocaine delivered under a low ratio schedule engendered response rates comparable to saline. However, increasing the ratio requirement resulted in large increases in responding for cocaine while responding for saline decreased. Mice self-administering cocaine displayed higher response rates at fixed ratio 5 and fixed ratio 20 compared to saline controls (two-way ANOVA, drug condition (F_(1,47) = 17.52, p = 0.0001); schedule F_(3,47) = 0.6405, p = 0.59; drug condition x schedule, F_{(3, 47)} = 3.381, p = 0.03). Sidak’s posttest: *p < 0.05; **p < 0.01 versus saline. Data represent mean ± SEM; n = 6 saline, n = 8 cocaine.