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bioRxiv · 10.1101/2023.06.08.544242

Punishment resistance for cocaine is associated with inflexible habits in rats

Jones, B. O.·Paladino, M. S.·Cruz, A. M.·Spencer, H. F.·Kahanek, P. L.·Scarborough, L. N.·Georges, S. F.·Smith, R. J.
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Abstract

Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration (2 h/day). We then exposed them to 4 days of punishment testing, in which footshock (0.4 mA, 0.3 s) was delivered randomly on one-third of trials, immediately following completion of seeking and prior to extension of the taking lever. Before and after punishment testing (4 days pre-punishment and [≥]4 days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.

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Jones, B. O., Paladino, M. S., Cruz, A. M., Spencer, H. F., Kahanek, P. L., Scarborough, L. N., Georges, S. F., Smith, R. J.. 2023-06-09. Punishment resistance for cocaine is associated with inflexible habits in rats. https://doi.org/10.1101/2023.06.08.544242

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