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

Abstract

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.

Making and breaking habits: Revisiting the definitions and behavioral factors that influence habits in animals

“…Random ratio (RR) and random interval (RI) schedules were shown to bias goal-directed or habitual responding, respectively (Dickinson et al, 1983). This finding has been replicated numerous times (Dickinson, 1985;Gremel & Costa, 2013;Hilario et al, 2012;Jones, Cruz, Kim, et al, 2022;Wiltgen et al, 2012;Yin et al, 2004;Yin, Ostlund, et al, 2005;. Although not as common, some instances of training on interval schedules have instead led to goal-directed expression (Corbit et al, 2014;Garr et al, 2020).…”

“…In this study, rats were trained to selfadminister cocaine on a seeking-taking chained schedule of reinforcement and then given four days of punishment testing in which footshock was delivered after seeking on a random one third of trials (Jones et al, 2023). To assess habitual behavior, the animals were tested with outcome devaluation via cocaine satiety (Jones, Cruz, Kim, et al, 2022) several days before and after punishment testing. Rats that were sensitive to punishment (i.e., reduced cocaine self-administration) showed goal-directed behavior in the postpunishment devaluation test, even if they were habitual in the prepunishment devaluation test (Jones et al, 2023).…”

“…However, further work indicated that the insensitivity of the distal link was not due to habitual responding but to a lack of incentive learning; the distal link showed sensitivity once animals had the opportunity to experience the food reward in the devalued state (Balleine et al, 1995(Balleine et al, , 2005. More recent work showed that sensitivity to outcome devaluation was correlated on the distal and proximal links (i.e., seeking and taking levers) in a seeking-taking chained schedule for intravenous cocaine responding (Jones, Cruz, Kim, et al, 2022). Further, for both cocaine and food responding, some animals showed sensitivity to outcome devaluation on the distal link of the chain, whereas other animals showed insensitivity, indicating that the distal link could be under goal-directed or habitual control (Jones, Cruz, Kim, et al, 2022).…”

“…For example, inactivation of DLS enhanced punishment sensitivity, suggesting that DLS plays a role in punishment resistance (Jonkman et al, 2012a). As DLS has been implicated in habitual responding for drug rewards (Belin et al, 2008;Corbit et al, 2012;Jones, Cruz, Kim, et al, 2022;Zapata et al, 2010), this may indicate a connection between habits and punishment resistance. In support of this, punishment resistance for alcohol was associated with alcohol seeking that had become habitual and DLS-dependent (Giuliano et al, 2019(Giuliano et al, , 2021.…”

“…Orally consumed drugs, like alcohol and oral cocaine, have been devalued using satiety or LiCl aversion (Corbit et al, 2012; Dickinson et al, 2002; Miles et al, 2003; Swanson et al, 2017), whereas intravenous cocaine or nicotine have been devalued using LiCl aversion (Clemens et al, 2014; Leong et al, 2016; Loughlin et al, 2017; Root et al, 2009) or extinguishing the taking link in a seeking‐taking chained schedule of reinforcement (Olmstead et al, 2001; Zapata et al, 2010). Although, a recent study established a procedure for outcome devaluation via satiety for intravenous cocaine (Jones, Cruz, Kim, et al, 2022).…”