Shift from goal-directed to habitual cocaine seeking after prolonged experience in rats

Abstract

The development of drug-seeking habits is implicated in the transition from recreational drug use to addiction. Using a drug seeking/taking chained schedule of intravenous cocaine self-administration and reward devaluation methods in rats, the present studies examined whether drug seeking that is initially goal-directed becomes habitual after prolonged drug seeking and taking. Devaluation of the outcome of the drug seeking link (i.e., the drug taking link of the chained schedule) by extinction significantly decreased drug seeking indicating that behavior is goal-directed rather than habitual. With, however, more prolonged drug experience, animals transitioned to habitual cocaine seeking. Thus, in these animals, cocaine seeking was insensitive to outcome devaluation. Moreover, when the dorsolateral striatum, an area implicated in habit learning, was transiently inactivated, outcome devaluation was effective in decreasing drug seeking indicating that responding was no longer habitual but had reverted to control by the goal-directed system. These studies provide direct evidence that cocaine seeking becomes habitual with prolonged drug experience and describe a rodent model with which to study the neural mechanisms underlying the transition from goal-directed to habitual drug seeking.

Figure 1.

A, Devaluation testing: experiment 1. After stable acquisition of the drug seeking/taking chained schedule, the cocaine taking link was devalued by extinction. Responses on the drug seeking lever and head entries into the sucrose magazine were measured under extinction conditions during 5 min tests before and after revaluation of the drug taking link (arrows) by two sessions where cocaine infusions were available again under an FR1 schedule. B, Cocaine seeking responses and head entries into the sucrose magazine during tests conducted under devalued and revalued conditions. C, The magnitude of the devaluation effect was calculated as cocaine seeking responses after devaluation expressed as a percentage of seeking responses under the revalued condition for each animal (filled circles, n = 14). Percentage of seeking responses under the revalued condition is plotted for each animal. The average ± SEM for the group (solid horizontal line) is also shown. All data are expressed as the mean ± SEM. *p < 0.05, paired t test.

Figure 2.

Effects of training duration on sensitivity to devaluation: experiment 2. A, Devaluation tests were performed after short training and again after extended training of the drug seeking/taking chained schedule (arrows). Cocaine seeking responses and head entries into the sucrose magazine for each session, consisting of 12 drug infusions, are shown. Dotted lines indicate each block of 3 daily sessions. The devaluation tests followed the same procedure as in experiment 1. B, Seeking responses for cocaine during the test. C, Head entries into the sucrose magazine during the test. D, The magnitude of the devaluation effect was calculated as cocaine seeking responses after devaluation expressed as a percentage of seeking responses under the revalued condition for each animal. Animals were assigned to two groups according to their sensitivity to devaluation after short training [3 animals showed no effect of devaluation (open circles) and 3 animals devalued 40% or more (filled circles)]. E, The average ± SEM devaluation effect for each of these groups is shown. All data are expressed as the mean ± SEM.

Figure 3.

Influence of transient inactivation of the dorsolateral striatum on devaluation: experiment 3. Devaluation testing was performed after an extended training procedure identical to that used in experiment 2. Animals were divided into 2 groups with similar performance during the drug seeking/taking schedule. A, Cocaine-seeking responses for each session, consisting of 12 drug infusions, are shown. Dotted lines separate each block of 3 daily sessions. The devaluation tests took place only at the end of the extended training (arrow) and followed the same procedure as in experiment 1, except that animals received infusions of aCSF or 4% lidocaine in the dorsolateral striatum immediately before the drug seeking tests. B, Cocaine seeking responses during testing. C, Head entries responses during testing. D, Histological reconstruction of cannula placements (open circles, aCSF; filled circles, 4% lidocaine). All data are mean ± SEM. Number of animals per group is shown in parenthesis. *p < 0.01, Student–Newman–Keuls post hoc test.