Differential vulnerability to the punishment of cocaine related behaviours: effects of locus of punishment, cocaine taking history and alternative reinforcer availability

Abstract

Background: The availability of alternative reinforcement has been shown to reduce drug use, but it remains unclear whether it facilitates a reduction or cessation of drug seeking or taking.

Objectives: We compared the effects of punishment of cocaine seeking or taking behaviour after brief or extended cocaine-taking histories when behavioural reallocation was facilitated or not by making available an alternative ingestive reinforcer (sucrose).

Methods: In the first experiment, punishment of either seeking or taking responses was introduced immediately after training on the seeking-taking chained schedule. In the second experiment, punishment of cocaine seeking was introduced after 12 additional days of either 1 or 6 h daily access to cocaine self-administration. In both experiments, beginning 1 week before the introduction of punishment, a subset of rats had concurrent nose poke access to sucrose while seeking or taking cocaine.

Results: The presence of an alternative source of reinforcement markedly facilitated behavioural reallocation from punished cocaine taking after acquisition. It also facilitated punishment-induced suppression of cocaine seeking after an extensive cocaine self-administration history likely by prompting goal-directed motivational control over drug use. However, a significant proportion of rats were deemed compulsive-maintaining drug use after an extensive cocaine history despite the presence of abstinence-promoting positive and negative incentives.

Conclusion: Making available an alternative reinforcer facilitates disengagement from punished cocaine use through at least two different processes but remains ineffective in a subpopulation of vulnerable animals, which continued to seek cocaine despite the aversive consequence of punishment and the presence of the alternative positive reinforcer.

Fig. 1

a The timeline of experiment 1. b Number of cycles completed before (baseline) and during punishment of sucrose taking (black triangles) or sucrose seeking responses after training on the sucrose seeking-taking task. c Number of cycles completed before (baseline) and during punishment of cocaine taking (grey dots) or cocaine seeking (white dots) responses after training on the cocaine seeking-taking task. d Number of cycles completed before (baseline) and during punishment of cocaine taking (black dots) or cocaine seeking (white dots) responses after training on the cocaine seeking-taking task with the availability concomitantly to nose poke for sucrose. e The number of nose poke responses for sucrose under baseline and punishment of the cocaine seeking or taking responses. Average ± SEM of 12 to 19 animals per group. *Tukey’s HSD; p < 0.05

Fig. 2

Total time per session taken to press on the taking lever (dark histograms) and to initiate (light histograms) and complete (grey histograms) the seeking link of the seeking-taking schedule when the taking (a) or the seeking (b) link was punished. Solid histograms represent the times when cocaine was the only source of reinforcement available and the hashed histograms when rats could concomitantly nose poke for sucrose. c The level of investment allocated to cocaine seeking (white dots) or taking (black dots) over motivated behaviours (see “Statistical analysesˮ section for further details) whether the cocaine responding was punished (solid lines) or not (hashed lines). Average ± SEM of 15 to 19 animals per group. *Difference with baseline, a differences between groups, Tukey’s HSD; p < 0.05

Fig. 3

a The timeline of experiment 2. Early loading phase (first hour) during free access sessions (b). Number of cycles completed before (baseline) and during punishment of cocaine seeking responding after 12 days of 1 h (ShA white dots) or 6 h (LgA black dots) cocaine access without (c) or with (d) the availability of sucrose following a nose poke response. e The number of nose poke responses for sucrose under baseline and punishment of cocaine seeking. Average ± SEM of 17 to 37 animals per group. *Differences between groups, Tukey’s HSD; p < 0.05, p < 0.05

Fig. 4

a Distributions of the mean number of seeking responses across the four last days of intermittent punishment of cocaine seeking responding in the “ShA” (white triangle), “LgA” (grey triangle), “ShA + sucrose” (white circle) and “LgA + sucrose” (grey circle) groups. b Proportion of compulsive animals in the ShA (grey histograms), “LgA” (black histogram), “ShA + sucrose” (waved grey histograms) and “LgA + sucrose” (waved black histograms) groups. c Mean number of seeking responses per session or d nose poke rate while seeking across the last 4 days of intermittent punishment of cocaine seeking responding in non-compulsive (grey borders) and compulsive (black borders) and after limited (grey histograms) or extended/escalated (black histograms) cocaine self-administration history. In c diamond-filled histograms represent the mean for the animals without (diamond histograms) and the circle-filled histogram with the availability to concomitantly nose poke for sucrose. Average ± SEM of 3 to 27 animals per group. *Tukey’s HSD; p < 0.05