Article Figures & Data
Figures
- Figure 1.
Timeline of cocaine self-administration and voltammetric recordings. A, Our experimental design yielded four groups: (1) rats that self-administered a single cocaine infusion with no prior cocaine experience [single injection (no history), black], (2) rats that performed 5 d of cocaine self-administration [cocaine, green], (3) rats that performed cocaine self-administration followed by a 14 or 60 d abstinence and were subsequently allowed to self-administer a single injection of saline [cocaine + abstinence, blue], and (4) rats that performed cocaine self-administration followed by a 14 or 60 d abstinence and were subsequently re-exposed to a single self-administered injection of cocaine (re-exposure, red). B, Number of reinforcers earned relative to day of acquisition. Lack of error post-acquisition reflects the session limit of 40 injections being reached by all rats. Inset, Average number of self-administration sessions before acquisition criteria were met. C, Over the course of cocaine self-administration rats escalate in rate of cocaine intake over days. ***p < 0.001 versus day 1. Error bars indicate ± SEM.
- Figure 2.
Cocaine self-administration-induced cocaine tolerance in the NAc core is reinstated by a single cocaine injection. A, Experimental timeline. B, Dopamine (DA), as indicated by current (z-axis) occurring at its oxidation (+0.6 V) and reduction (−0.2 V) peaks (y-axis) across time (x-axis) is represented as pseudo-color plots following 30 μm cocaine. Representative color plots and traces (C) show that the ability of cocaine to slow dopamine uptake is blunted in rats with a history of cocaine self-administration, and after cocaine re-exposure. Logarithmic (D) and linear (E) concentration–response curves for cocaine show a downward shift in cocaine effects in the cocaine and re-exposure groups. F, Ki values for cocaine are increased in the cocaine and re-exposure groups, indicating decreased cocaine potency at the DAT. *p < 0.05, ***p < 0.001 versus control. Control, n = 4; single injection, n = 4; cocaine, n = 5; cocaine + 14 days off, n = 5; re-exposure at Day 14, n = 8. Error bars indicate ± SEM.
- Figure 3.
Cocaine self-administration leaves the DAT in a labile state following prolonged abstinence. A, Experimental timeline showing binge cocaine self-administration and subsequent cocaine re-exposure following a 60 d abstinence period. B, Dopamine (DA), as indicated by current (z-axis) occurring at its oxidation (+0.6 V) and reduction (−0.2 V) peaks (y-axis) across time (x-axis) is represented as pseudo-color plots and traces (C) following 30 μm cocaine. Logarithmic (D) and linear (E) cocaine concentration–response curves indicate tolerance to the uptake inhibiting effects of cocaine following cocaine self-administration, and this tolerance is reinstated by a single cocaine injection following a 60 d abstinence period. F, Ki values for cocaine are increased (ie, decreased cocaine potency) in the cocaine and re-exposure groups. *p < 0.05, **p < 0.01, ***p < 0.001 versus control. Control, n = 7; single injection, n = 4; cocaine, n = 6; cocaine + 60 days off, n = 6; re-exposure at Day 60, n = 6. Error bars indicate ± SEM.
- Figure 4.
Cocaine re-exposure produces tolerance to the locomotor-activating effects of cocaine. A, Experimental timeline. Rats performed cocaine self-administration followed by a 60 d abstinence period before subsequent re-exposure to a cocaine challenge (15 mg/kg, i.p.). B, Rats with a history of cocaine self-administration show tolerance to the locomotor activating effects of cocaine, with no change in spontaneous locomotor activity. C, Area under the locomotor activity curve following the cocaine challenge is decreased in rats with a history of cocaine self-administration. *p < 0.05, **p < 0.01, ***p < 0.001 versus re-exposure group. Control, n = 5; re-exposure at Day 60, n = 6. Error bars indicate ± SEM.
- Figure 5.
Escalated rate of cocaine intake remains following abstinence. A, Experimental timeline. Rats performed 5 d of cocaine or saline self-administration before a 14 d abstinence period. Both groups were then allowed to self-administer cocaine for 5 d post-abstinence. B, Control rats did not escalate in rate of intake during the saline self-administration period, but did escalate during 5 d of cocaine self-administration after abstinence. Conversely, re-exposure rats escalated during the initial 5 d of self-administration, but did not continue to escalate following the abstinence period. C, Rate of cocaine intake did not differ between the final day of pre-abstinence self-administration and the first day of post-abstinence self-administration in the re-exposure group. *p < 0.05, **p < 0.01 for the slope of the regression line versus zero. Control, n = 5; re-exposure, n = 7. Error bars indicate ± SEM.
