Seeking-taking chain schedules of cocaine and sucrose self-administration: effects of reward size, reward omission, and α-flupenthixol

Abstract

Rationale: In heterogeneous seeking-taking (ST) chain schedules of self-administration, seeking rewards and taking rewards are distinct actions, giving animals explicit control over their intake of the reward. However, the neurobehavioral characteristics of ST chain schedules are relatively unexplored.

Objectives: This study was made to evaluate two variants of ST chain schedules of self-administration to measure seeking and taking of sucrose and cocaine in rats.

Methods: Rats had to respond on one lever (seeking lever) under a random interval (RI) or under a progressive ratio (PR) schedule, to gain access to a second lever (taking lever), responding on which under a fixed-ratio 1 (FR-1) schedule of reinforcement delivered the reward. We assessed the effects of reward size, reward omission, and administration of the dopamine receptor antagonist α-flupenthixol. The effects of α-flupenthixol on responding for cocaine or sucrose under an FR-1 schedule of reinforcement were also assessed.

Results: Cocaine seeking under both schedules was reduced by decreasing reward size, reward omission, and α-flupenthixol treatment. Cocaine taking was decreased by α-flupenthixol treatment and reward omission, but not by altering reward size. Sucrose seeking was not affected by reward size, but was reduced by α-flupenthixol and reward omission. Sucrose taking was diminished by reward omission only. α-Flupenthixol increased cocaine but not sucrose intake under an FR-1 schedule of reinforcement.

Conclusions: Both ST(PR) and ST(RI) schedules can be used to assess seeking and taking of sucrose and cocaine. Dopaminergic neurotransmission mediates the positive subjective properties of cocaine but not sucrose and the motivational properties of both sucrose and cocaine.

Fig. 1

Effect of altering reward size, α-flupenthixol, and reward omission on responding for cocaine under an ST(RI-120) schedule in rats. a Seeking response rates for different unit doses of cocaine (n = 12). b Number of taking responses for different unit doses of cocaine (n = 12). c Effect of α-flupenthixol on cocaine seeking (n = 10). d Effect of α-flupenthixol on cocaine taking (n = 10). e Effects of reward omission and reacquisition on cocaine seeking: baseline response (session 0; closed symbol) followed by 10 reward omission sessions (sessions 1–10; open symbols), followed by reacquisition (sessions 11–15; closed symbols) (n = 15). f Effects of reward omission and reacquisition on cocaine taking: baseline response (session 0; closed symbol) followed by 10 reward omission sessions (sessions 1–10; open symbols), followed by reacquisition (sessions 11–15; closed symbols) (n = 15). Data are presented as mean presses/min ± SEM (seeking) or mean ± SEM taking responses. *p < 0.05 for difference between groups (a–d) or sessions (e, f) (paired t test)

Fig. 2

Effect of altering reward size, α-flupenthixol, and reward omission on responding for cocaine under an ST(PR) schedule in rats. a Breakpoints for different unit doses of cocaine (n = 7). b Effect of α-flupenthixol on breakpoints for cocaine (n = 10). c Effects of reward omission and reacquisition on breakpoints; baseline response (session 0; closed symbol) followed by three reward omission sessions (sessions 1–3; open symbols), after which reacquisition took place (session 4; closed symbols) (n = 8). Data are presented as mean breakpoints ± SEM. *p < 0.05 for difference between groups (a, b) or sessions (c) (Wilcoxon signed ranks test)

Fig. 3

Effect of altering reward size, α-flupenthixol, and reward omission on responding for sucrose under an ST(RI-120) schedule in rats. a Seeking response rates for different amounts of sucrose pellets (n = 10). b Number of taking responses for different amounts of sucrose pellets (n = 10). c Effect of α-flupenthixol on sucrose seeking (n = 10). d Effect of α-flupenthixol on sucrose taking (n = 10). e Effects of reward omission and reacquisition on sucrose seeking: baseline response (session 0; closed symbol) followed by 10 reward omission sessions (sessions 1–10; open symbols), after which reacquisition took place (sessions 11–14; closed symbols) (n = 9). f Effects of reward omission and reacquisition on sucrose taking: baseline response (session 0; closed symbol) followed by 10 reward omission sessions (sessions 1–10; open symbols), after which reacquisition took place (sessions 11–14; closed symbols) (n = 9). Data are presented as mean presses/min ± SEM (seeking) or mean ± SEM taking responses. *p < 0.05 for difference between groups (a–d) or sessions (e, f) (paired t test)

Fig. 4

Effect of altering reward size, α-flupenthixol, and reward omission on responding for sucrose under an ST(PR) schedule in rats. a Breakpoints for different amounts of sucrose pellets (n = 10). b Effect of α-flupenthixol on breakpoints for sucrose (n = 10). c Effects of reward omission and reacquisition on breakpoints; baseline response (session 0; closed symbol) followed by 20 reward omission sessions (sessions 1–20; open symbols), after which reacquisition took place (sessions 21–25; closed symbols) (n = 10). Data are presented in mean breakpoints ± SEM. *p < 0.05 for difference between groups (a, b) or sessions (c) (Wilcoxon signed ranks test)

Fig. 5

Effect of α-flupenthixol on responding for cocaine (a) and sucrose (b) under an FR-1 schedule of reinforcement. Data are presented in mean number of lever presses ± SEM. *p < 0.05 for difference compared to vehicle treatment (paired t test)