Discriminating goal-directed and habitual cocaine seeking in rats using a novel outcome devaluation procedure

• Published in: Learning & memory (Cold Spring Harbor, N.Y.) N.Y.), 2022-12, Vol.29 (12), p.447-457
• Main Authors: Jones, Bradley O, Cruz, Adelis M, Kim, Tabitha H, Spencer, Haley F, Smith, Rachel J
• Format: Article
• Language: English
• Subjects: Animals; Cocaine; Conditioning, Operant; Extinction, Psychological; Goals; Male; Motivation; Rats; Research Paper
• ISSN: 1549-5485; 1072-0502; 1549-5485
• DOI: 10.1101/lm.053621.122

Habits are theorized to play a key role in compulsive cocaine seeking, yet there is limited methodology for assessing habitual responding for intravenous (IV) cocaine. We developed a novel outcome devaluation procedure to discriminate goal-directed from habitual responding in cocaine-seeking rats. This procedure elicits devaluation temporarily and requires no additional training, allowing repeated testing at different time points. After training male rats to self-administer IV cocaine, we devalued the drug outcome via experimenter-administered IV cocaine (a "satiety" procedure) prior to a 10-min extinction test. Many rats were sensitive to outcome devaluation, a hallmark of goal-directed responding. These animals reduced responding when given a dose of experimenter-administered cocaine that matched or exceeded satiety levels during self-administration. However, other rats were insensitive to experimenter-administered cocaine, suggesting their responding was habitual. Importantly, reinforcement schedules and neural manipulations that produce goal-directed responding (i.e., ratio schedules or dorsolateral striatum lesions) caused sensitivity to outcome devaluation, whereas reinforcement schedules and neural manipulations that produce habitual responding (i.e., interval schedules or dorsomedial striatum lesions) caused insensitivity. Satiety-based outcome devaluation is an innovative new tool to dissect the neural and behavioral mechanisms underlying IV cocaine-seeking behavior.